Medical device and method for manufacturing same

ABSTRACT

A medical device includes: a substrate layer; an adhesive layer formed on at least a part of the substrate layer and containing a hydrophilic copolymer (1) containing a structural unit derived from a polymerizable monomer (A) having a sulfobetaine structure, a structural unit derived from a polymerizable monomer (B) having at least one group selected from the group consisting of a sulfonic acid group (—SO 3 H), a sulfuric acid group (—OSO 3 H), a sulfurous acid group (—OSO 2 H), and salt groups thereof, and a structural unit derived from a polymerizable monomer (C) having a photoreactive group; and a surface lubricious layer formed on at least a part of the adhesive layer and containing a polymer containing a structural unit derived from acrylamide and a hydrophilic copolymer (2).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/JP2020/031640 filed on Aug. 21, 2020, which claims priority toJapanese Patent Application No. 2019-151583, filed on Aug. 21, 2019, theentire content of both of which is incorporated herein by reference.

TECHNOLOGICAL FIELD

The disclosure here relates to a medical device and a method formanufacturing the same. In particular, the disclosure relates to amedical device including a surface lubricious layer exhibiting anexcellent lubricating property and a method for manufacturing the same.

BACKGROUND DISCUSSION

In recent years, a catheter with a reduced outer diameter has been usedto improve insertion to a peripheral portion of a blood vessel, and isthereby used for diagnosis and treatment of various lesion sites.Therefore, in the diagnosis or the treatment using the catheter, aclearance between the catheter and an inner surface of a lumen in aliving body is extremely small, which may result in high frictionalresistance on a surface of the catheter. Therefore, the catheter isrequired to include a coating that imparts a lubricating property anddurability (lubrication retaining property) to the surface of thecatheter.

For example, WO 2018/038063 (corresponding to US 2019/0185776 A1)discloses that a hydrophilic copolymer is used for a surface lubriciouslayer, the hydrophilic copolymer containing a structural unit derivedfrom a polymerizable monomer (A) having a sulfobetaine structure, astructural unit derived from a polymerizable monomer (B) having a groupsuch as a sulfonic acid group, and a structural unit derived from apolymerizable monomer (C) having a photoreactive group.

SUMMARY

The surface lubricious layer disclosed in WO 2018/038063 (correspondingto US 2019/0185776 A1) certainly exhibits an excellent lubricatingproperty and excellent durability (lubrication retaining property). Onthe other hand, a medical technique for advancing a more flexiblemedical device to a narrower lesion site in a living body becomeswidespread, and in recent years, a demand for operability for making themedical device reach the lesion site increases. Therefore, a techniquefor further improving the lubricating property in order to operate themedical device satisfactorily even in a narrower lesion site isdemanded.

The disclosure here provides a way for improving the lubricatingproperty.

The present inventor has made diligent studies to solve the aboveproblem. As a result, the present inventor has found that the aboveproblem can be solved by providing, on a substrate layer, an adhesivelayer containing a hydrophilic copolymer containing specific structuralunits and a surface lubricious layer containing a hydrophilic copolymercontaining specific structural units and a polymer containing astructural unit derived from acrylamide, and has thus completed thediscovery described below.

Disclosed here is a medical device including: a substrate layer; anadhesive layer formed on at least a part of the substrate layer andcontaining a hydrophilic copolymer (1) containing a structural unitderived from a polymerizable monomer (A) having a sulfobetainestructure, a structural unit derived from a polymerizable monomer (B)having at least one group selected from the group consisting of asulfonic acid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurousacid group (—OSO₂H), and salt groups thereof, and a structural unitderived from a polymerizable monomer (C) having a photoreactive group;and a surface lubricious layer formed on at least a part of the adhesivelayer and containing a polymer containing a structural unit derived fromacrylamide and a hydrophilic copolymer (2) containing a structural unitderived from a polymerizable monomer (A′) having a sulfobetainestructure, a structural unit derived from a polymerizable monomer (B′)having at least one group selected from the group consisting of asulfonic acid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurousacid group (—OSO₂H), and salt groups thereof, and a structural unitderived from a polymerizable monomer (C′) having a photoreactive group.

Another aspect involves a method comprising inserting a medical deviceinto a lumen in a living body. The medical device comprises a substratelayer and an adhesive layer formed on at least a part of the substratelayer. The adhesive layer contains a hydrophilic copolymer (1)containing (i) a structural unit derived from a polymerizable monomer(A) having a sulfobetaine structure, (ii) a structural unit derived froma polymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group, a sulfuric acid group, asulfurous acid group, and salt groups thereof, and (iii) a structuralunit derived from a polymerizable monomer (C) having a photoreactivegroup. The medical device further includes a surface lubricious layerformed on at least a part of the adhesive layer. The surface lubriciouslayer contains a polymer, said polymer containing (a) a structural unitderived from acrylamide, and (b) a hydrophilic copolymer (2) containing(i) a structural unit derived from a polymerizable monomer (A′) having asulfobetaine structure, (ii) a structural unit derived from apolymerizable monomer (B′) having at least one group selected from thegroup consisting of a sulfonic acid group, a sulfuric acid group, asulfurous acid group, and salt groups thereof, and (iii) a structuralunit derived from a polymerizable monomer (C′) having a photoreactivegroup. The method further involves moving the medical device in thelumen in the living body, whereby aqueous liquid in the lumen contactsand wets the surface lubricious layer so that the surface lubriciouslayer exhibits a lubricating property. In a yet further aspect themedical device is a catheter, a stent, or a guide wire.

A further aspect disclosed here involves a method for manufacturing amedical device comprising: applying a coating liquid (1) onto asubstrate to form an adhesive layer on the substrate, and applying acoating liquid (2) onto the adhesive layer to form a surface lubriciouslayer. The coating liquid (1) comprises: a hydrophilic copolymer (1)containing: i) a structural unit derived from a polymerizable monomer(A) having a sulfobetaine structure; ii) a structural unit derived froma polymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group, a sulfuric acid group, asulfurous acid group, and salt groups thereof; and iii) a structuralunit derived from a polymerizable monomer (C) having a photoreactivegroup. The coating liquid (2) comprises a polymer containing: (a) astructural unit derived from acrylamide; and (b) a hydrophilic copolymer(2), the hydrophilic copolymer (2) containing: i) a structural unitderived from a polymerizable monomer (A′) having a sulfobetainestructure; ii) a structural unit derived from a polymerizable monomer(B′) having at least one group selected from the group consisting of asulfonic acid group, a sulfuric acid group, a sulfurous acid group, andsalt groups thereof; and iii) a structural unit derived from apolymerizable monomer (C′) having a photoreactive group.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partial cross-sectional view schematically showing a surfacelamination structure of a medical device according to an exemplaryembodiment of the medical device.

FIG. 2 is a partial cross-sectional view schematically showing aconfiguration example having a different surface lamination structure asan application example of the embodiment in FIG. 1.

FIG. 3 is a schematic view showing a lubricating property and durabilitytest device (friction meter) used in Examples and Comparative Examples.

FIG. 4 is a graph showing lubricating property and durability testresults in Example 1 and Comparative Example 1.

DETAILED DESCRIPTION

Set forth below with reference to the accompanying drawings is adetailed description of embodiments of a medical device andmanufacturing method representing examples of the inventive catheterdisclosed herein. The invention is not limited to the followingembodiments. In the present description, “X to Y” indicating a rangeincludes X and Y, and means “X or more and Y or less”. In the presentdescription, “X and/or Y” means to include at least one of X and Y, andincludes “X alone”, “Y alone”, and “a combination of X and Y”. Unlessotherwise specified, operations, measurements of physical properties,and the like are performed under conditions of room temperature (20° C.to 25° C.) and a relative humidity of 40% to 60% RH.

In the present description, the term “(meth)acrylic” includes bothacrylic and methacrylic. Therefore, for example, the term “(meth)acrylicacid” includes both acrylic acid and methacrylic acid. Similarly, theterm “(meth)acryloyl” includes both acryloyl and methacryloyl.Therefore, for example, the term “(meth)acryloyl group” includes both anacryloyl group and a methacryloyl group.

In the present description, unless otherwise specified, the term“substituted” refers to being substituted with a C1 to C30 alkyl group,a C2 to C30 alkenyl group, a C2 to C30 alkynyl group, a C1 to C30 alkoxygroup, an alkoxycarbonyl group (—COOR, R represents a C1 to C30 alkylgroup), a halogen atom (F, Cl, Br, or I atom), a C6 to C30 aryl group, aC6 to C30 aryloxy group, an amino group, a C1 to C30 alkylamino group, acyano group, a nitro group, a thiol group, a C1 to C30 alkylthio group,or a hydroxy group. Note that, when a group is substituted, asubstitution in which a structure after substitution falls under adefinition before the substitution is excluded. For example, when asubstituent is an alkyl group, this alkyl group as a substituent is notfurther substituted with another alkyl group.

In the present description, a “polymerizable monomer (A) having asulfobetaine structure” is also simply referred to as a “polymerizablemonomer (A)” or a “polymerizable monomer (A) according to theinvention”. Similarly, a “structural unit derived from a polymerizablemonomer (A) having a sulfobetaine structure” is also simply referred toas a “structural unit (A)” or a “structural unit (A) according to theinvention”. Similarly, in the present description, a “polymerizablemonomer (A′) having a sulfobetaine structure” is also simply referred toas a “polymerizable monomer (A′)” or a “polymerizable monomer (A′)according to the invention”. Similarly, a “structural unit derived froma polymerizable monomer (A′) having a sulfobetaine structure” is alsosimply referred to as a “structural unit (A′)” or a “structural unit(A′) according to the invention”.

In the present description, a “polymerizable monomer (B) having at leastone group selected from the group consisting of a sulfonic acid group(—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof” is also simply referred to as a“polymerizable monomer (B)” or a “polymerizable monomer (B) according tothe invention”. Similarly, a “structural unit derived from apolymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof” isalso simply referred to as a “structural unit (B)” or a “structural unit(B) according to the invention”. Similarly, in the present description,a “polymerizable monomer (B′) having at least one group selected fromthe group consisting of a sulfonic acid group (—SO₃H), a sulfuric acidgroup (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groupsthereof” is also simply referred to as a “polymerizable monomer (B′)” ora “polymerizable monomer (B′) according to the invention”. Similarly, a“structural unit derived from a polymerizable monomer (B′) having atleast one group selected from the group consisting of a sulfonic acidgroup (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof” is also simply referred to as a“structural unit (B′)” or a “structural unit (B′) according to theinvention”.

In the present description, a “polymerizable monomer (C) having aphotoreactive group” is also simply referred to as a “polymerizablemonomer (C)” or a “polymerizable monomer (C) according to theinvention”. Similarly, a “structural unit derived from a polymerizablemonomer (C) having a photoreactive group” is also simply referred to asa “structural unit (C)” or a “structural unit (C) according to theinvention”. Similarly, in the present description, a “polymerizablemonomer (C′) having a photoreactive group” is also simply referred to asa “polymerizable monomer (C′)” or a “polymerizable monomer (C′)according to the invention”. Similarly, a “structural unit derived froma polymerizable monomer (C′) having a photoreactive group” is alsosimply referred to as a “structural unit (C′)” or a “structural unit(C′) according to the invention”.

In the present description, a “hydrophilic copolymer (1) containing astructural unit (A), a structural unit (B), and a structural unit (C)”is also simply referred to as a “hydrophilic copolymer (1)” or a“hydrophilic copolymer (1) according to the invention”. Similarly, inthe present description, a “hydrophilic copolymer (2) containing astructural unit (A′), a structural unit (B′), and a structural unit(C′)” is also simply referred to as a “hydrophilic copolymer (2)” or a“hydrophilic copolymer (2) according to the invention”.

In the present description, a “polymerizable monomer” is also simplyreferred to as a “monomer”.

In the present description, a “structural unit derived from acrylamide”is also simply referred to as an “acrylamide structural unit”. A“polymer containing a structural unit derived from acrylamide” is alsosimply referred to as an “acrylamide-based polymer”.

In the present description, when a structural unit is said to be“derived” from a monomer, it means that the structural unit is adivalent structural unit generated by a polymerizable unsaturated doublebond (C═C) present in the monomer corresponding to the structural unitbecoming a single bond (—C—C—).

According to a first aspect, a medical device is provided, the medicaldevice including: a substrate layer; an adhesive layer formed on atleast a part of the substrate layer and containing a hydrophiliccopolymer (1) containing a structural unit derived from a polymerizablemonomer (A) having a sulfobetaine structure, a structural unit derivedfrom a polymerizable monomer (B) having at least one group selected fromthe group consisting of a sulfonic acid group (—SO₃H), a sulfuric acidgroup (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groupsthereof, and a structural unit derived from a polymerizable monomer (C)having a photoreactive group; and a surface lubricious layer formed onat least a part of the adhesive layer and containing a polymercontaining a structural unit derived from acrylamide and a hydrophiliccopolymer (2) containing a structural unit derived from a polymerizablemonomer (A′) having a sulfobetaine structure, a structural unit derivedfrom a polymerizable monomer (B′) having at least one group selectedfrom the group consisting of a sulfonic acid group (—SO₃H), a sulfuricacid group (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groupsthereof, and a structural unit derived from a polymerizable monomer (C′)having a photoreactive group. The medical device having the aboveconfiguration can exhibit an excellent lubricating property.

In recent years, miniaturization and diameter reduction of medicaldevices have advanced, and a medical technique for advancing a moreflexible medical device to a narrower lesion site in a living body hasbecome widespread. A device that can maintain good operability even in asite where a clearance between the medical device and an inner surfaceof a lumen in the living body is small is demanded. The present inventorhas made diligent studies to meet such a demand. As a result, thepresent inventor has found that a high lubricating property can beexhibited even under a high load condition (that is, even in a sitewhere the clearance between the medical device and the inner surface ofthe lumen in the living body is small) by using the surface lubriciouslayer described in the above WO 2018/038063 (corresponding to US2019/0185776 A1) as an adhesive layer and providing, on the adhesivelayer, a surface lubricious layer containing a hydrophilic copolymer anda polymer containing a structural unit derived from acrylamide. Amechanism by which such an effect is produced is unclear, but thefollowing mechanism is theorized. Note that the following mechanism istheory, and the invention is not limited to the following theory.Specifically, the surface lubricious layer contains the hydrophiliccopolymer (hydrophilic copolymer (2)) and the polymer containing astructural unit derived from acrylamide. Here, the hydrophilic copolymer(hydrophilic copolymer (2)) contained in the surface lubricious layerexhibits a lubricating property when wet (for example, when in contactwith an aqueous liquid such as a body fluid or physiological saline). Inaddition, the polymer containing a structural unit derived fromacrylamide has a water retention effect (acts as a water-retainingmaterial). In such a surface lubricious layer, in addition to a waterabsorption effect of the water-retaining material, a crosslink densityis moderately low due to presence of the water-retaining material.Therefore, the aqueous liquid easily enters the surface lubricious layer(the hydrophilic copolymer (2) easily exhibits a lubricating property(surface gel hydration lubrication) when in contact with the aqueousliquid). Under a high load condition, the surface lubricious layerdisclosed here can maintain a sufficient hydrated layer on a surface ofthe medical device due to the aqueous liquid retained on the surfacelubricious layer. Therefore, it is considered that the hydrophiliccopolymer (2) can exhibit a sufficient lubricating property even under ahigh load condition.

The hydrophilic copolymer (1) in the adhesive layer and the hydrophiliccopolymer (2) in the surface lubricious layer each have a photoreactivegroup. When the adhesive layer or the surface lubricious layer isirradiated with active energy rays, the photoreactive group generatesreactive species, and the hydrophilic copolymer (1) in the adhesivelayer reacts with the substrate layer (resin) to form a covalent bondbetween the substrate layer and the adhesive layer. In addition, due tothe generation of these reactive species, the hydrophilic copolymer (1)in the adhesive layer reacts with the hydrophilic copolymer (2) or thepolymer containing a structural unit derived from acrylamide in thesurface lubricious layer, so that a covalent bond is also formed betweenthe adhesive layer and the surface lubricious layer. Accordingly,according to the disclosure, by providing the adhesive layer between thesubstrate layer and the surface lubricious layer, the surface lubriciouslayer can be firmly immobilized to the substrate layer via the adhesivelayer. Therefore, the medical device according to the disclosure canmaintain an initial lubricating property for a longer period of time andhave further improved durability (lubrication retaining property).

Therefore, the medical device according to the disclosure can exhibit anexcellent lubricating property even under a condition where theclearance between the medical device and the inner surface of the lumenin the living body is small (high load condition). In addition, themedical device according to the disclosure can exhibit excellentdurability (lubrication retaining property).

Hereinafter, a preferred embodiment of the medical device disclosed herewill be described with reference to the attached drawings.

FIG. 1 is a partial cross-sectional view schematically showing a surfacelamination structure of a medical device according to an exemplaryembodiment of the medical device (hereinafter, also simply referred toas a “medical device”). FIG. 2 is a partial cross-sectional viewschematically showing a configuration example having a different surfacelamination structure as an application example in the presentembodiment. Note that in FIG. 1 and FIG. 2, 1 represents a substratelayer, 1 a represents a substrate layer core portion, 1 b represents asubstrate surface layer, 2 represents an adhesive layer, 3 represents asurface lubricious layer, and 10 represents a medical device.

As shown in FIG. 1 and FIG. 2, the medical device 10 according to thepresent embodiment includes: the substrate layer 1; the adhesive layer 2containing the hydrophilic copolymer (1) and immobilized (disposed) soas to cover at least a part of a surface of the substrate layer 1 (inthe drawing, an example of being immobilized (disposed) on the wholesurface (entire surface) of the substrate layer 1 in the drawing isshown); and the surface lubricious layer 3 containing the hydrophiliccopolymer (2) and a polymer containing a structural unit derived fromacrylamide and immobilized (disposed) so as to cover at least a part ofa surface of the adhesive layer 2 (in the drawing, an example of beingimmobilized (disposed) on the whole surface (entire surface) of theadhesive layer 2 in the drawing is shown). The adhesive layer 2 isbonded to the substrate layer 1 and the hydrophilic copolymer (2) andthe polymer containing a structural unit derived from acrylamide in thesurface lubricious layer 3 via the photoreactive group of thehydrophilic copolymer (1).

Hereinafter, each configuration of the medical device according to thepresent embodiment will be described.

The disclosure relates to a medical device, the medical deviceincluding: a substrate layer; an adhesive layer formed on at least apart of the substrate layer and containing a hydrophilic copolymer (1)containing a structural unit derived from a polymerizable monomer (A)having a sulfobetaine structure, a structural unit derived from apolymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof, anda structural unit derived from a polymerizable monomer (C) having aphotoreactive group; and a surface lubricious layer formed on at least apart of the adhesive layer and containing a polymer containing astructural unit derived from acrylamide and a hydrophilic copolymer (2)containing a structural unit derived from a polymerizable monomer (A′)having a sulfobetaine structure, a structural unit derived from apolymerizable monomer (B′) having at least one group selected from thegroup consisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof, anda structural unit derived from a polymerizable monomer (C′) having aphotoreactive group.

[Substrate Layer (Substrate)]

The substrate layer used in this aspect may be constituted by anymaterial as long as the material can react with the photoreactive groupcontained in the hydrophilic copolymer (1), which will be describedlater, to form a chemical bond. Specifically, examples of the materialconstituting (forming) the substrate layer 1 include a metal material, apolymer material, ceramics. Here, as shown in FIG. 1, the substratelayer 1 may be entirely (wholly) constituted (formed) by any one of theabove materials, or, as shown in FIG. 2, the substrate layer 1 may havea configuration in which a surface of the substrate layer core portion 1a constituted (formed) by any one of the above materials is covered(coated) with any other of the above materials by an appropriate methodto constitute (form) the substrate surface layer 1 b. Examples of thelatter case include a configuration in which a metal material is covered(coated) by an appropriate method (a known method in the related artsuch as plating, metal deposition, and sputtering) on the surface of thesubstrate layer core portion 1 a formed by a resin material or the liketo form the substrate surface layer 1 b, and a configuration in which onthe surface of the substrate layer core portion 1 a formed by a hardreinforcing material such as a metal material or a ceramic material, apolymer material that is more flexible than the reinforcing materialsuch as a metal material is covered (coated) by an appropriate method (aknown method in the related art such as dipping, spraying, coating, andprinting), or the reinforcing material of the substrate layer coreportion 1 a and the polymer material of the substrate surface layer 1 bare com posited (an appropriate reaction treatment), so as to form thesubstrate surface layer 1 b. Therefore, the substrate layer core portion1 a may be a multilayer structure in which different materials arelaminated in multiple layers, a structure (composite) in which membersmade of different materials for each part of the medical device areconnected to each other, or the like. Another middle layer (not shown)may be formed between the substrate layer core portion 1 a and thesubstrate surface layer 1 b. The substrate surface layer 1 b may also bea multilayer structure in which different materials are laminated inmultiple layers, a structure (composite) in which members made ofdifferent materials for each part of the medical device are connected toeach other, or the like.

Among the materials constituting (forming) the above substrate layer 1,the metal material is not particularly limited, and metal materialscommonly used in medical devices such as a catheter, a stent and a guidewire are used. Specific examples thereof include various stainlesssteels (SUS) such as SUS304, SUS316, SUS316L, SUS420J2, and SUS630,gold, platinum, silver, copper, nickel, cobalt, titanium, iron,aluminum, tin, and various alloys such as a nickel-titanium (Ni—Ti)alloy, a nickel-cobalt (Ni—Co) alloy, a cobalt-chromium (Co—Cr) alloy,and a zinc-tungsten (Zn—W) alloy. These metal materials may be usedalone or in combination of two or more types thereof. The most suitablemetal material as a substrate layer for a catheter, a stent, a guidewire, or the like, which is the intended use, may be appropriatelyselected for the above metal materials.

Among the materials constituting (forming) the above substrate layer 1,the polymer material is not particularly limited, and polymer materialscommonly used in medical devices such as a catheter, a stent and a guidewire are used. Specific examples thereof include polyamide resins,polyethylenes such as a linear low density polyethylene (LLDPE), a lowdensity polyethylene (LDPE), a high density polyethylene (HDPE), and amodified polyethylene, polyolefin resins such as polypropylene,polyester resins such as polyethylene terephthalate, polystyrene resinssuch as polystyrene, cyclic polyolefin resins, modified polyolefinresins, epoxy resins, urethane resins, diallyl phthalate resins (allylresin), polycarbonate resins, fluororesin, amino resins (a urea resin, amelamine resin, and a benzoguanamine resin), acrylic resins, polyacetalresins, vinyl acetate resins, phenol resins, vinyl chloride resins,silicone resins (silicon resins), polyether resins such aspolyetheretherketone (PEEK), and polyimide resins. From the viewpoint ofadhesiveness to the adhesive layer described later, polyethylenes suchas a high density polyethylene (HDPE) and a modified polyethylene,polyether resins such as polyetheretherketone (PEEK), and polyamideresins are preferred. These polymer materials may be used alone or incombination of two or more types thereof. The most suitable polymermaterial as a substrate layer for a catheter, a stent, a guide wire, orthe like, which is the intended use, may be appropriately selected forthe above polymer materials.

A shape of the above substrate layer is not particularly limited, and isappropriately selected as a sheet shape, a linear (wire) shape, atubular shape, and the like depending on the form of the substrate layerto be used.

[Adhesive Layer (Hydrophilic Copolymer (1))]

The adhesive layer is formed on at least a part of the substrate layerand contains the hydrophilic copolymer (1) containing the structuralunit derived from the polymerizable monomer (A) having a sulfobetainestructure (structural unit (A)), the structural unit derived from thepolymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof(structural unit (B)), and the structural unit derived from thepolymerizable monomer (C) having a photoreactive group (structural unit(C)). Here, the adhesive layer is not necessarily formed on the entiresurface of the substrate layer. For example, the adhesive layer may beformed on a surface portion (a part) of the substrate layer to be incontact with the body fluid.

The hydrophilic copolymer (1) contained in the adhesive layer accordingto the disclosure contains the structural unit (the structural unit (A))derived from the polymerizable monomer (A) (hereinafter, also referredto as a “monomer A”) having a sulfobetaine structure, the structuralunit (the structural unit (B)) derived from the polymerizable monomer(B) (hereinafter, also referred to as a “monomer B”) having at least onegroup selected from the group consisting of a sulfonic acid group(—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof, and the structural unit (thestructural unit (C)) derived from the polymerizable monomer (C)(hereinafter, also referred to as a “monomer C”) having a photoreactivegroup. The hydrophilic copolymer (1) (hence, the adhesive layer) canexhibit a sufficient lubricating property and sufficient durability(lubrication retaining property). The hydrophilic copolymer (1) has goodbondability (adhesiveness) to the substrate layer and the hydrophiliccopolymer (2) or the polymer containing a structural unit derived fromacrylamide as the water-retaining material in the surface lubriciouslayer described later. A mechanism by which such an effect is producedis not completely unclear, but the following mechanism is theorized. Thephotoreactive group contained in the structural unit derived from themonomer C generates reactive species by the irradiation with the activeenergy rays, and reacts with the surface of the substrate layer and thehydrophilic copolymer (2) or the polymer containing a structural unitderived from acrylamide in the surface lubricious layer described laterto form a chemical bond. Therefore, the adhesive layer containing thehydrophilic copolymer (1) according to the disclosure is firmlyimmobilized on the substrate layer, and firmly immobilizes the surfacelubricious layer, so that the durability (lubrication retainingproperty) is excellent. Note that the above mechanism is theory, and theinvention is not limited to the above theory.

In the medical device, another layer may be provided between theadhesive layer and the substrate layer as long as another layer does notinfluence functions and effects of the medical device, and preferably,the adhesive layer is directly disposed above the substrate layer.

A thickness of the adhesive layer is not particularly limited. From theviewpoints of the adhesiveness to the substrate layer, the adhesivenessto the surface lubricious layer, the lubricating property, and the like,the thickness (dry film thickness) of the adhesive layer is preferably0.1 μm to 100 μm, and more preferably 0.2 μm to 50 μm.

Hereinafter, each polymerizable monomer constituting the hydrophiliccopolymer (1) contained in the adhesive layer according to thedisclosure will be described.

(Polymerizable Monomer (A))

The hydrophilic copolymer (1) contains the structural unit derived fromthe polymerizable monomer (A) having a sulfobetaine structure(structural unit (A)). Here, the structural unit (A) constituting thehydrophilic copolymer (1) may be one type alone or a combination of twoor more types. That is, the structural unit (A) may be constituted byonly one type of structural unit (A), or may be constituted by two ormore types of structural units (A). Note that a plurality of structuralunits (A) may be present in a block shape or in a random shape.

The polymerizable monomer (A) (monomer A) is a polymerizable monomerhaving a sulfobetaine structure. The sulfobetaine structure included inthe structural unit derived from the monomer A is excellent in effect ofimparting the lubricating property. Therefore, the hydrophilic copolymer(1) containing the structural unit derived from the monomer A isconsidered to be excellent in lubricating property. A homopolymer of themonomer A is soluble in an aqueous NaCl solution, but is insoluble ordifficult to dissolve in water or a lower alcohol. Therefore, it issuggested that the sulfobetaine structure may have a strongelectrostatic interaction. Therefore, a strong cohesive force actsinside the adhesive layer containing the hydrophilic copolymer (1)according to the disclosure. Accordingly, the adhesive layer isconsidered to have high strength (excellent in durability). Note thatthe above is theory, and the invention is not limited to the abovetheory.

Here, the “sulfobetaine structure” refers to a structure in which apositive charge and a negative charge containing a sulfur element arepresent in positions not adjacent to each other, a dissociable hydrogenatom is not bonded to an atom having the positive charge, and a sum ofthe charges is zero.

The monomer A is not particularly limited, and examples thereof includecompounds represented by the following general formulas.

In the above general formulas, R^(a) and R^(d) may each independentlyrepresent a substitutable alkylene group having 1 to 30 carbon atoms ora substitutable arylene group having 6 to 30 carbon atoms. R^(b) andR^(c) may each independently represent a substitutable alkyl grouphaving 1 to 30 carbon atoms or a substitutable aryl group having 6 to 30carbon atoms. Y may represent a group having an ethylenicallyunsaturated group such as an acryloyl group (CH₂═CH—C(═O)—), amethacryloyl group (CH₂═C(CH₃)—C(═O)—), and a vinyl group (CH₂═CH—).Here, in the above general formulas, the sum of the positive charges andthe negative charges is zero.

Examples of the alkylene group having 1 to 30 carbon atoms include amethylene group, an ethylene group, a trimethylene group, a propylenegroup, an isopropylene group, a butylene group, an isobutylene group, asec-butylene group, a tert-butylene group, and a pentylene group.

Examples of the arylene group having 6 to 30 carbon atoms include aphenylene group, a naphthylene group, an anthracenylene group, aphenanthrenylene group, a pyrenylene group, a peryleneylene group, afluorenylene group, and a biphenylene group.

Examples of the alkyl group having 1 to 30 carbon atoms include a methylgroup, an ethyl group, a n-propyl group, an isopropyl group, a n-butylgroup, an isobutyl group, a sec-butyl group, a tert-butyl group, an-pentyl group, an iso-amyl group, a tert-pentyl group, a neopentylgroup, and a n-hexyl group.

Examples of the aryl group having 6 to 30 carbon atoms include a phenylgroup, a biphenyl group, a terphenyl group, a pentarenyl group, anindenyl group, a naphthyl group, an azulenyl group, a heptalenyl group,and a biphenylenyl group.

Among these, from the viewpoint of further improving the lubricatingproperty and the durability (lubrication retaining property), themonomer A is preferably a compound represented by the following formula(1). That is, in a preferred embodiment of the medical device, thepolymerizable monomer (A) is a compound represented by the followingformula (1).

In the above formula (1), R¹¹ represents a hydrogen atom or a methylgroup. Z¹ represents an oxygen atom (—O—) or —NH—, and preferably anoxygen atom (—O—).

In the above formula (1), from the viewpoint of further improving thelubricating property and the durability (lubrication retainingproperty), R¹² and R¹⁵ each independently represent a linear or branchedalkylene group having 1 to 20 carbon atoms, preferably a linear orbranched alkylene group having 1 to 12 carbon atoms, more preferably alinear or branched alkylene group having 1 to 8 carbon atoms, still morepreferably a linear or branched alkylene group having 1 to 6 carbonatoms, even more preferably a linear alkylene group having 1 to 4 carbonatoms (methylene group, ethylene group, trimethylene group, ortetramethylene group), and particularly preferably a linear alkylenegroup having 1 to 3 carbon atoms (methylene group, ethylene group, ortrimethylene group). From the viewpoint of further improving thelubricating property and the durability (lubrication retainingproperty), as a combination of R¹² and R¹⁵, R¹² preferably represents anethylene group and R¹⁵ preferably represents a trimethylene group, orR¹² preferably represents a trimethylene group and R¹⁵ preferablyrepresents a tetramethylene group.

In the above formula (1), from the viewpoint of further improving thelubricating property and the durability (lubrication retainingproperty), R¹³ and R¹⁴ each independently represent a linear or branchedalkyl group having 1 to 20 carbon atoms, preferably a linear or branchedalkyl group having 1 to 12 carbon atoms, more preferably a linear orbranched alkyl group having 1 to 8 carbon atoms, still more preferably alinear or branched alkyl group having 1 to 4 carbon atoms, andparticularly preferably a methyl group.

Examples of the compound represented by the above formula (1) include{2-[(meth)acryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide,{2-[(meth)acryloyloxy]ethyl}dimethyl-(2-sulfoethyl)ammonium hydroxide,{2-[(meth)acryloyloxy]ethyl}dimethyl-(2-sulfobutyl)ammonium hydroxide,{2-[(meth)acryloyloxy]ethyl}diethyl-(2-sulfoethyl)ammonium hydroxide,{2-[(meth)acryloyloxy]ethyl}diethyl-(3-sulfopropyl)ammonium hydroxide,{2-[(meth)acryloyloxy]ethyl}diethyl-(2-sulfobutyl)ammonium hydroxide,{3-[(meth)acryloyloxy]propyl}dimethyl-(2-sulfoethyl)ammonium hydroxide,{3-[(meth)acryloyloxy]propyl}dimethyl-(3-sulfopropyl)ammonium hydroxide,{3-[(meth)acryloylamino)propyl}dimethyl(3-sulfobutyl)ammonium hydroxide,{3-[(meth)acryloyloxy]propyl}diethyl-(2-sulfoethyl)ammonium hydroxide,{3-[(meth)acryloyloxy]propyl}diethyl-(3-sulfopropyl)ammonium hydroxide,and {3-[(meth)acryloyloxy]propyl}diethyl-(3-sulfobutyl)ammoniumhydroxide. Among these,{2-[(meth)acryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxideand {3-[(meth)acryloyloxy)propyl]dimethyl(3-sulfobutyl)ammoniumhydroxide are preferred,{2-[methacryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide(MSPB) and [3-(methacryloylamino)propyl]dimethyl(3-sulfobutyl)ammoniumhydroxide (MSBB) are more preferred, and{2-[methacryloyloxy]ethyl}dimethyl-(3-sulfopropyl)ammonium hydroxide(MSPB) is still more preferred. The above compounds may be used alone orin combination of two or more types thereof.

As the monomer A, either a synthetic product or a commercially availableproduct may be used. The commercially available product is availablefrom Sigma-Aldrich Co. LLC., Fujifilm Wako Pure Chemical Cooperation,and the like. An exemplary compound may be synthesized with reference toA. Laschewsky, polymers, 6, 1544-1601 (2014), and the like.

The monomer A is not limited to the compounds represented by the abovegeneral formulas, and may be a compound having a form in which apositive charge is present at a terminal end.

In the hydrophilic copolymer (1), when a total of structural unitsderived from all the monomers is 100 mol %, a content of the structuralunit derived from the monomer A is preferably 0.1 mol % to 99 mol %,more preferably 1 mol % to 99 mol %, still more preferably 5 mol % to 99mol %, and particularly preferably 10 mol % to 99 mol %. Within such arange, a balance between the lubricating property and the solventsolubility is good. Note that when the structural unit (A) isconstituted by two or more types of structural units (A), a compositionof the above structural unit (A) occupies a ratio (molar ratio (mol %))of all the structural units (A) with respect to the total of thestructural units derived from all the monomers (100 mol %). The mol % issubstantially equivalent to a ratio of a charge amount (mol) of themonomer A with respect to a total charge amount (mol) of all themonomers in the production of the polymer.

(Polymerizable Monomer (B))

The hydrophilic copolymer (1) contains the structural unit derived fromthe polymerizable monomer (B) having at least one group selected fromthe group consisting of a sulfonic acid group (—SO₃H), a sulfuric acidgroup (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof(structural unit (B)). Here, the structural unit (B) constituting thehydrophilic copolymer (1) may be one type alone or a combination of twoor more types. That is, the structural unit (B) may be constituted byonly one type of structural unit (B), or may be constituted by two ormore types of structural units (B). Note that a plurality of structuralunits (B) may be present in a block shape or in a random shape.

The polymerizable monomer (B) (monomer B) is a polymerizable monomerhaving at least one group selected from the group consisting of asulfonic acid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurousacid group (—OSO₂H), and salt groups thereof. By introducing such agroup, anionization occurs in an aqueous solvent, and electrostaticrepulsion occurs between the hydrophilic copolymers. As a result, anelectrostatic interaction between the sulfobetaine structures and ahydrophobic interaction between the photoreactive groups in thehydrophilic copolymers are reduced. Therefore, the solvent solubility ofthe copolymer (particularly the solubility in water, a lower alcohol, ora mixed solvent of water and a lower alcohol) is improved. Thisimproving effect is particularly remarkable when the photoreactive groupof the monomer C is a benzophenone group. Since the benzophenone grouphas a plurality of aromatic rings, the benzophenone groups are likely toassociate with each other by a π-π interaction, which makes the polymerscontaining the benzophenone group to aggregate and insolubilize.Therefore, it is considered that by introducing the structural unitderived from the monomer B, the electrostatic repulsion occurs asdescribed above, and the association between the benzophenone groups isreduced, and thus the solubility or dispersibility of the polymer israpidly improved. Note that the above mechanism is theory, and theinvention is not limited to the above theory. Alternatively, even whenthe monomer C has an ester group, the above improving effect can beobtained satisfactorily. In addition to the above groups, the monomer Bpreferably has an ethylenically unsaturated group such as a(meth)acryloyl group, a vinyl group, or an allyl group.

Among these, from the viewpoint of further improving the solventsolubility, the monomer (B) is preferably a compound represented by thefollowing formula (2), (3), or (4), and more preferably a compoundrepresented by the following formula (2). That is, in a preferredembodiment of the medical device, the polymerizable monomer (B) is acompound represented by the following formula (2), (3), or (4). In amore preferred embodiment of the medical device, the polymerizablemonomer (B) is a compound represented by the following formula (2).

In the above formula (2), R²¹ represents a hydrogen atom or a methylgroup. Z² represents an oxygen atom (—O—) or —NH—, and preferably —NH—.

In the above formula (2), from the viewpoint of further improving thesolvent solubility, R²² represents a linear or branched alkylene grouphaving 1 to 20 carbon atoms, preferably a linear or branched alkylenegroup having 1 to 12 carbon atoms, more preferably a linear or branchedalkylene group having 1 to 8 carbon atoms, still more preferably alinear or branched alkylene group having 1 to 6 carbon atoms, andparticularly preferably a branched alkylene group having 3 to 5 carbonatoms. The branched alkylene group having 3 to 5 carbon atoms is a grouprepresented by —CH(CH₃)—CH₂—, —C(CH₃)₂—CH₂—, —CH(CH₃)—CH(CH₃)—,—C(CH₃)₂—CH₂—CH₂—, —CH(CH₃)—CH(CH₃)—CH₂—, —CH(CH₃)—CH₂—CH(CH₃)—,—CH₂—C(CH₃)₂—CH₂—, —C(CH₃)₂—CH(CH₃)—, or the like (a connection order ofthe above groups in the above formula (2) is not particularly limited),and among these, a group represented by —C(CH₃)₂—CH₂— is particularlypreferred.

In the above formula (2), X represents a group selected from the groupconsisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof. Fromthe viewpoints of acid dissociation (that is, ease of anionization) andeven the solvent solubility of the copolymer, X preferably represents agroup selected from the group consisting of a sulfonic acid group, asulfuric acid group, and salt groups thereof. From the viewpoint of easyavailability of monomers, X more preferably represents a sulfonic acidgroup or a salt group thereof. Here, the salt is not particularlylimited, and for example, the salt may be an alkali metal salt (sodiumsalt, potassium salt, or the like) of the above group.

Examples of the compound represented by the above formula (2) include2-(meth)acrylamide-2-methyl-1-propanesulfonic acid,1-[(meth)acryloyloxymethyl]-1-propanesulfonic acid,2-[(meth)acryloyloxy]-2-propanesulfonic acid,3-[(meth)acryloyloxy]-1-methyl-1-propanesulfonic acid, 2-sulfoethyl(meth)acrylate, 3-sulfopropyl (meth)acrylate, and salts thereof(preferably a sodium salt or a potassium salt). Among these,2-(meth)acrylamide-2-methyl-1-propanesulfonic acid or a salt thereof(particularly alkali metal salt) is preferred, and2-acrylamide-2-methyl-1-propanesulfonic acid or a salt thereof(particularly sodium salt) is more preferred. These compounds may beused alone or in combination of two or more types thereof.

The compound represented by the above formula (2) may be either asynthetic product or a commercially available product, and thecommercially available product is available from Tokyo Chemical IndustryCo., Ltd., Sigma-Aldrich Co. LLC., and the like.

In the above formula (3), R³¹ represents a hydrogen atom or a methylgroup.

In the above formula (3), R³² represents a single bond or a linear orbranched alkylene group having 1 to 20 carbon atoms, preferably a singlebond or a linear or branched alkylene group having 1 to 12 carbon atoms,more preferably a single bond or a linear or branched alkylene grouphaving 1 to 8 carbon atoms, still more preferably a single bond or alinear or branched alkylene group having 1 to 4 carbon atoms, andparticularly preferably a single bond. Here, since specific examples ofthe alkylene group are the same as those for the above formula (2),description thereof will be omitted here.

In the above formula (3), X represents a group selected from the groupconsisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof. Fromthe viewpoints of the acid dissociation (that is, the ease ofanionization) and even the solvent solubility of the copolymer, Xpreferably represents a group selected from the group consisting of asulfonic acid group, a sulfuric acid group, and salt groups thereof.From the viewpoint of easy availability of monomers, X more preferablyrepresents a sulfonic acid group or a salt group thereof.

Examples of the compound represented by the above formula (3) includevinyl sulfonic acid, allyl sulfonic acid, methallyl sulfonic acid,2-propene-1-sulfonic acid, 2-methyl-2-propene-1-sulfonic acid, and saltsthereof. These compounds may be used alone or in combination of two ormore types thereof.

The compound represented by the above formula (3) may be either asynthetic product or a commercially available product, and thecommercially available product is available from Asahi Kasei FinechemCo., Ltd., Tokyo Chemical Industry Co., Ltd. (for example, sodium saltof 2-methyl-2-propene-1-sulfonic acid), and the like.

In the above formula (4), R⁴¹ represents a hydrogen atom or a methylgroup.

In the above formula (4), R⁴² represents a linear or branched alkylenegroup having 1 to 20 carbon atoms, preferably a linear or branchedalkylene group having 1 to 12 carbon atoms, more preferably a linear orbranched alkylene group having 1 to 8 carbon atoms, and still morepreferably a linear or branched alkylene group having 1 to 6 carbonatoms. Here, since specific examples of the alkylene group are the sameas those for the above formula (2), description thereof will be omittedhere.

In the above formula (4), X represents a group selected from the groupconsisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof. Fromthe viewpoints of the acid dissociation (that is, the ease ofanionization) and even the solvent solubility of the copolymer, Xpreferably represents a group selected from the group consisting of asulfonic acid group, a sulfuric acid group, and salt groups thereof.From the viewpoint of easy availability of monomers, X more preferablyrepresents a sulfonic acid group or a salt group thereof.

Examples of the compound represented by the above formula (4) include2-sulfoxyethyl vinyl ether, 3-sulfoxy-n-propyl vinyl ether, and saltsthereof. These compounds may be used alone or in combination of two ormore types thereof.

As the compound represented by the above formula (4), either a syntheticproduct or a commercially available product may be used.

In the hydrophilic copolymer (1), when the total of the structural unitsderived from all the monomers is 100 mol %, a content of the structuralunit derived from the monomer B is preferably 0.1 mol % to 99 mol %,more preferably 0.2 mol % to 99 mol %, still more preferably 0.5 mol %to 99 mol %, and particularly preferably 1 mol % to 99 mol %. Withinsuch a range, the balance between the lubricating property and thesolvent solubility is good. Note that when the structural unit (B) isconstituted by two or more types of structural units (B), a compositionof the above structural unit (B) occupies a ratio (molar ratio (mol %))of all the structural units (B) with respect to the total of thestructural units derived from all the monomers (100 mol %). The mol % issubstantially equivalent to a ratio of a charge amount (mol) of themonomer B with respect to the total charge amount (mol) of all themonomers in the production of the polymer.

(Polymerizable Monomer (C))

The hydrophilic copolymer (1) contains the structural unit derived fromthe polymerizable monomer (C) having a photoreactive group (structuralunit (C)). Here, the structural unit (C) constituting the hydrophiliccopolymer (1) may be one type alone or a combination of two or moretypes. That is, the structural unit (C) may be constituted by only onetype of structural unit (C), or may be constituted by two or more typesof structural units (C). Note that a plurality of structural units (C)may be present in a block shape or in a random shape.

The polymerizable monomer (C) (monomer C) is a polymerizable monomerhaving a photoreactive group. Here, the “photoreactive group” refers toa group that can generate reactive species such as radicals, nitrenes,and carbenes by being irradiated with active energy rays and react withthe substrate layer (resin) and the surface lubricious layer (thehydrophilic copolymer (2) and the polymer containing a structural unitderived from acrylamide) to form a chemical bond. Accordingly, theadhesive layer containing the hydrophilic copolymer (1) can firmlyimmobilize the substrate layer and the surface of the surface lubriciouslayer. Therefore, by disposing the adhesive layer between the substratelayer and the surface lubricious layer, the medical device can exhibitsufficient durability (lubrication retaining property). The monomer Cpreferably has an ethylenically unsaturated group such as a(meth)acryloyl group, a vinyl group, or an allyl group, in addition tothe above photoreactive group.

Examples of the photoreactive group include an azide group, a diazogroup, a diazirine group, a ketone group, and a quinone group.

Examples of the azide group include an aryl azide group of phenyl azideand 4-fluoro-3-nitrophenyl azide, an acyl azide group of benzoyl azideand p-methylbenzoyl azide, an azidoformate group of ethyl azideformateand phenyl azideformate, a sulfonyl azide group of benzenesulfonylazide, and a phosphoryl azide group of diphenylphosphoryl azide anddiethyl phosphoryl azide.

Examples of the diazo group include a group derived from diazoalkanessuch as diazomethane and diphenyldiazomethane, diazoketones such asdiazoacetophenone and 1-trifluoromethyl-1-diazo-2-pentanone,diazoacetates such as t-butyldiazoacetate and phenyldiazoacetate, anda-diazoacetoacetates such as t-butyl-α-diazoacetoacetate.

Examples of the diazirine group include a group derived from3-trifluoromethyl-3-phenyldiazirine.

Examples of the ketone group include a group having a structure such asacetophenone, benzophenone, anthrone, xanthine, and thioxanthone.

Examples of the quinone group include a group derived fromanthraquinone.

These photoreactive groups are appropriately selected depending on thetype of the substrate layer of the medical device and the like. Forexample, when the substrate layer is made of a polyolefin resin such asa polyethylene resin, a polyamide resin, a polyurethane resin, apolyester resin, or the like, the photoreactive group is preferably aketone group or a phenyl azide group, and more preferably a group havinga benzophenone structure (a benzophenone group) from the viewpoint ofeasy availability of monomers. That is, in a preferred embodiment of themedical device, the polymerizable monomer (C) has a group having abenzophenone structure.

Examples of the monomer C include 2-azidoethyl(meth)acrylate,2-azidopropyl(meth)acrylate, 3-azidopropyl(meth)acrylate,4-azidobutyl(meth)acrylate, 4-(meth)acryloyloxybenzophenone (MBP),4-(meth)acryloyloxyethoxybenzophenone,4-(meth)acryloyloxy-4′-methoxybenzophenone, 4-(meth)acryloyloxyethoxy-4′-methoxybenzophenone,4-(meth)acryloyloxy-4′-bromobenzophenone,4-(meth)acryloyloxyethoxy-4′-bromobenzophenone,4-styrylmethoxybenzophenone, 4-(meth)acryloyloxythioxanthone, and2-(meth)achryloyloxyethyl-4-azidobenzoate.

As the monomer C, either a synthetic product or a commercially availableproduct may be used, and the commercially available product is availablefrom MCC UNITEC Co., Ltd. or the like.

In the hydrophilic copolymer (1), when the total of the structural unitsderived from all the monomers is 100 mol %, a content of the structuralunit derived from the monomer C is preferably 0.1 mol % to 40 mol %,more preferably 0.1 mol % to 30 mol %, still more preferably 0.1 mol %to 25 mol %, and particularly preferably 0.1 mol % to 20 mol %. Withinsuch a range, the hydrophilic copolymer (1) can be sufficiently bondedto the substrate layer (resin) and the surface lubricious layer (thehydrophilic copolymer (2) and the polymer containing a structural unitderived from acrylamide). Accordingly, the adhesive layer containing thehydrophilic copolymer (1) can immobilize the substrate layer and thesurface lubricious layer more firmly. Within such a range, a sufficientamount of other monomers (the monomers A and B) can be present, so thatthe sufficient lubricating property and the durability by the monomer Aand the solvent solubility by the monomer B in the hydrophilic copolymer(1) can be more effectively improved. Note that when the structural unit(C) is constituted by two or more types of structural units (C), acomposition of the above structural unit (C) occupies a ratio (molarratio (mol %)) of all the structural units (C) with respect to the totalof the structural units derived from all the monomers (100 mol %). Themol % is substantially equivalent to a ratio of a charge amount (mol) ofthe monomer C with respect to the total charge amount (mol) of all themonomers in the production of the polymer.

The hydrophilic copolymer (1) may contain a structural unit derived froma polymerizable monomer other than the above monomer A, monomer B, andmonomer C (hereinafter, also referred to as “other monomer”) in a rangethat does not impair the effects of the medical device. In thehydrophilic copolymer (1) according to the disclosure, a content of thestructural unit derived from the other monomer is preferably less than10 mol %, more preferably less than 5 mol %, and still more preferablyless than 1 mol % (lower limit: more than 0 mol %), with respect to 100mol %, which is the total of the structural units derived from all themonomers. Note that when the structural unit derived from the othermonomer is constituted by two or more types of structural units, acomposition of the above structural unit derived from the other monomeroccupies a ratio (molar ratio (mol %)) of all the structural unitsderived from the other monomer with respect to the total of thestructural units derived from all the monomers (100 mol %). Preferably,the hydrophilic copolymer (1) according to the disclosure is constitutedonly by the monomer A, the monomer B, and the monomer C (the compositionof the other monomer =0 mol %). Note that the mol % is substantiallyequivalent to a ratio of a charge amount (mol) of the other monomer withrespect to the total charge amount (mol) of all the monomers in theproduction of the polymer.

A terminal end of the hydrophilic copolymer (1) is not particularlylimited and is appropriately defined depending on types of raw materialsto be used, and is usually a hydrogen atom. A structure of the copolymeris not particularly limited, and may be any of a random copolymer, analternating copolymer, a periodic copolymer, and a block copolymer.

A weight average molecular weight (Mw) of the hydrophilic copolymer (1)is preferably several thousand to several million, more preferably 1,000to 1,000,000, and particularly preferably 5,000 to 500,000. In thedisclosure, the “weight average molecular weight” shall be a valuemeasured by gel permeation chromatography (GPC) using polyethyleneglycol as a standard substance.

[Method for Manufacturing Hydrophilic Copolymer (1)]

A method for manufacturing the hydrophilic copolymer (1) is notparticularly limited, and known polymerization methods such as radicalpolymerization, anionic polymerization, and cationic polymerization canbe adopted. The radical polymerization that is easy in production ispreferably used.

As the polymerization method, a method of copolymerizing the abovemonomer A, monomer B, monomer C, and if necessary, the other monomer bystirring and heating together with a polymerization initiator in apolymerization solvent is usually adopted.

A polymerization temperature is not particularly limited, and ispreferably 25° C. to 100° C., and more preferably 30° C. to 80° C. Apolymerization time is also not particularly limited, and is preferably30 minutes to 24 hours, and more preferably 1 hour to 8 hours.

The polymerization solvent is preferably water, and an aqueous solventsuch as alcohols such as methanol, ethanol, propanol, n-butanol, and2,2,2-trifluoroethanol. From the viewpoint of dissolving raw materialsto be used for the polymerization, these polymerization solvents may beused alone or in combination of two or more types thereof.

A concentration of the polymerizable monomers is not particularlylimited, and a total solid content (g) of each polymerizable monomerwith respect to the polymerization solvent (mL) is preferably 0.05 g/mLto 1 g/mL, and more preferably 0.1 g/mL to 0.5 g/mL. The preferred ratioof the charge amount (mol) of each monomer to the total charge amount(mol) of all the monomers is as described above.

A reaction solution containing the polymerizable monomers may besubjected to a degassing treatment before the polymerization initiatoris added. The degassing treatment may be performed by, for example,bubbling the reaction solution with an inert gas such as nitrogen gasand argon gas for approximately 0.5 hours to 5 hours. During thedegassing treatment, the reaction solution may be heated toapproximately 30° C. to 100° C.

Known polymerization initiators in the related art can be used in theproduction of the polymer, and the polymerization initiator is notparticularly limited. For example, an azo-based polymerization initiatorsuch as 2,2′-azobisisobutyronitrile,2,2′-azobis(4-methoxy-2,4-dimethylvaleronitrile),4,4′-azobis(4-cyanovaleric acid), and2,2′-azobis(2,4-dimethylvaleronitrile), and a redox-based polymerizationinitiator in which a reducing agent such as sodium sulfite, sodiumhydrogen sulfite, and ascorbic acid is combined with an oxidizing agentsuch as a persulfate such as potassium persulfate (KPS), sodiumpersulfate, and ammonium persulfate, and a peroxide such as hydrogenperoxide, t-butyl peroxide, and methyl ethyl ketone peroxide can beused.

A blending amount of the polymerization initiator is preferably 0.001mol % to 10 mol %, and more preferably 0.01 mol % to 5 mol % withrespect to a total amount (mol) of the polymerizable monomers.

Further, if necessary, a chain transfer agent, a polymerization rateadjusting agent, a surfactant, and other additives may be appropriatelyused in the polymerization.

An atmosphere in which the polymerization reaction is performed is notparticularly limited, and the polymerization reaction can be performedin air atmosphere, an atmosphere of an inert gas such as nitrogen gasand argon gas, and the like. During the polymerization reaction, thereaction solution may be stirred.

The copolymer may be precipitated during the polymerization reaction.The copolymer after polymerization can be purified by a generalpurification method such as a reprecipitation method, a dialysis method,an ultrafiltration method, and an extraction method.

The copolymer after purification can be dried by any method such asfreeze drying, vacuum drying, spray drying, and heat drying, and fromthe viewpoint of having a small influence on physical properties of thepolymer, freeze drying or vacuum drying is preferred.

Unreacted monomers contained in the obtained copolymer are preferably0.01 wt % or less with respect to the total amount of the copolymer. Asmaller amount of unreacted monomers is preferred (lower limit: 0 wt %).A content of the remaining monomers can be measured by a known methodsuch as high performance liquid chromatography.

The presence and the ratio of the structural unit derived from eachpolymerizable monomer in the hydrophilic copolymer (1) in the adhesivelayer can be confirmed by, for example, analyzing peak intensity of agroup contained in each structural unit using a known method such as IR,NMR, and pyrolysis GC/MS. In the present description, the presence andthe ratio of the structural unit derived from each polymerizable monomerin the hydrophilic copolymer (1) in the adhesive layer are measuredaccording to the following method.

(Method for Detecting and Measuring Presence and Ratio of StructuralUnit Derived from Each Polymerizable Monomer in Hydrophilic Copolymer(1) in Adhesive Layer)

With the surface of the medical device swollen with heavy water or thelike, precision diagonal cutting is performed on the medical device toprepare an inclined cross section of the medical device. From the crosssection, an adhesive layer portion located near the substrate of themedical device is cut, and a material of the adhesive layer portion iscollected. Next, the material of the adhesive layer portion is filledinto a sample tube for solid NMR without any gap to prepare a sample,and NMR measurement is performed. Here, peaks specific to a site (forexample, a sulfobetaine structure) specific to the structural unit (A),a site (for example, a salt of a sulfonic acid group) specific to thestructural unit (B), and a site (for example, a benzophenone group)specific to the structural unit (C) are to be confirmed, and when thesepeaks are confirmed, it is determined that the corresponding structuralunits are present in the sample. A concentration of the site (forexample, the sulfobetaine structure) specific to the structural unit (A)(concentration (a)), a concentration of the site (for example, the saltof the sulfonic acid group) specific to the structural unit (B)(concentration (b)), and a concentration of the site (for example, thebenzophenone group) specific to the structural unit (C) (concentration(c)) are measured. A ratio of each of the concentrations (a), (b), and(c) is regarded as an abundance ratio of the structural unit derivedfrom each polymerizable monomer in the hydrophilic copolymer (1). Notethat an analyzer and measurement conditions used in the abovemeasurement are as follows.

Analyzer: NM080006, manufactured by JEOL Ltd. Measurement conditions:heavy water or a mixed liquid of heavy water and a heavy solvent of alower alcohol.

[Surface Lubricious Layer]

The surface lubricious layer in the medical device is formed on at leasta part of the adhesive layer and contains (i) the polymer containing astructural unit derived from acrylamide, and (ii) the hydrophiliccopolymer (2) containing the structural unit derived from thepolymerizable monomer (A′) having a sulfobetaine structure, thestructural unit derived from the polymerizable monomer (B′) having atleast one group selected from the group consisting of a sulfonic acidgroup (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof, and the structural unit derived fromthe polymerizable monomer (C′) having a photoreactive group. Here, thesurface lubricious layer is not necessarily formed on the entire surfaceof the adhesive layer. The surface lubricious layer may be formed on asurface portion (a part) of the adhesive layer to be in contact with abody fluid, and is preferably formed on the entire surface of theadhesive layer.

The surface lubricious layer contains (i) the polymer containing astructural unit derived from acrylamide (acrylamide-based polymer) and(ii) the hydrophilic copolymer (2). Of these, (ii) the hydrophiliccopolymer (2) exhibits a lubricating property when wet (for example,when in contact with an aqueous liquid such as a body fluid orphysiological saline). (i) The acrylamide-based polymer acts to retainthe aqueous liquid. The presence of the acrylamide-based polymermoderately reduces the crosslink density of the surface lubriciouslayer. Therefore, the aqueous liquid easily enters the surfacelubricious layer, and the hydrophilic copolymer (2) easily exhibits alubricating property (gel hydration lubrication). In addition, under ahigh load condition, the surface lubricious layer forms a hydrated layerbetween the inner surface of the lumen in the living body and themedical device due to the aqueous liquid retained on the surfacelubricious layer. Therefore, it is considered that the hydrophiliccopolymer (2) can exhibit a lubricating property by being in contactwith a sufficient amount of the aqueous liquid even under a high loadcondition. Note that the above mechanism is theory, and the invention isnot limited to the above theory.

In the medical device, another layer may be provided between the surfacelubricious layer and the adhesive layer as long as another layer doesnot influence functions and effects of the medical device, andpreferably, the surface lubricious layer is directly disposed above theadhesive layer. In addition, another layer may be provided on thesurface lubricious layer as long as the functions and effects of themedical device are not influenced, and it is preferable that anotherlayer is not disposed on the surface lubricious layer (the surfacelubricious layer is an outermost layer). According to this embodiment,the effect (lubricating property) of the medical device can beeffectively exhibited.

A thickness of the surface lubricious layer is not particularly limited.From the viewpoints of the lubricating property, the durability(lubrication retaining property), the adhesiveness to the adhesivelayer, and the like, the thickness (dry film thickness) of the surfacelubricious layer is preferably 0.1 μm to 100 μm, and more preferably 0.2μm to 50 μm.

Hereinafter, compositions (the polymer containing a structural unitderived from acrylamide and the hydrophilic copolymer (2)) contained inthe surface lubricious layer according to the disclosure will bedescribed.

(Polymer Containing Structural Unit Derived from Acrylamide)

The surface lubricious layer contains the polymer containing astructural unit derived from acrylamide (acrylamide structural unit),i.e., the following formula (acrylamide-based polymer).

The polymer containing a structural unit derived from acrylamide maycontain a structural unit derived from another monomer, in addition tothe above acrylamide structural unit. Here, another monomer that may becontained when the acrylamide-based polymer contains the structural unitderived from another monomer is not particularly limited as long asanother monomer does not inhibit the water retention effect. Specificexamples thereof include N,N-dimethylacrylamide, N-isopropylacrylamide,vinylpyrrolidone, acrylic acid, and acrylates (for example, sodium saltand potassium salt). Here, the structural unit derived from the aboveanother monomer may be one type alone or a combination of two or moretypes. That is, the structural unit derived from another monomer may beconstituted by only one type of structural unit, or may be constitutedby two or more types of structural units. Note that a plurality ofstructural units derived from another monomer may be present in a blockshape or in a random shape. In this embodiment, a content of thestructural unit derived from another monomer is preferably less than 10mol %, more preferably less than 5 mol %, and still more preferably lessthan 1 mol % (lower limit: 0 mol %), with respect to 100 mol %, which isthe total of the structural units derived from all the monomers. Notethat the mol % is substantially equivalent to a ratio of a charge amount(mol) of another monomer with respect to the total charge amount (mol)of all the monomers in the production of the polymer. Preferably, thepolymer containing a structural unit derived from acrylamide accordingto the disclosure (acrylamide-based polymer) is preferably constitutedby only acrylamide. That is, in a preferred embodiment of the medicaldevice, the polymer containing a structural unit derived from acrylamideis polyacrylamide.

A molecular weight of the polymer containing a structural unit derivedfrom acrylamide is not particularly limited. For example, a numberaverage molecular weight (Mn) of the polymer containing a structuralunit derived from acrylamide is 500 to 50,000,000, preferably 1,000 to25,000,000, more preferably 1,000 to 20,000,000, still more preferably5,000 to 10,000,000, particularly preferably 10,000 to 5,000,000, andmost preferably 10,000 to 2,000,000. The acrylamide-based polymer insuch a range can exhibit a sufficient water retention effect. In thedisclosure, the “number average molecular weight” shall be a valuemeasured by gel permeation chromatography (GPC) using polyethyleneglycol as a standard substance.

As the polymer containing a structural unit derived from acrylamide,either a synthetic product or a commercially available product may beused. The commercially available product is available from Sigma-AldrichCo. LLC. and the like.

(Hydrophilic Copolymer (2))

The surface lubricious layer contains the hydrophilic copolymer (2) inaddition to the polymer containing a structural unit derived fromacrylamide. The hydrophilic copolymer (2) contains the structural unitderived from the polymerizable monomer (A′) having a sulfobetainestructure, the structural unit derived from the polymerizable monomer(B′) having at least one group selected from the group consisting of asulfonic acid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurousacid group (—OSO₂H), and salt groups thereof, and the structural unitderived from the polymerizable monomer (C′) having a photoreactivegroup. The hydrophilic copolymer (2) contained in the surface lubriciouslayer may have a structure same as or different from that of thehydrophilic copolymer (1) contained in the adhesive layer. From theviewpoint of immobilization strength (hence durability) between theadhesive layer and the surface lubricious layer, the hydrophiliccopolymer (1) and the hydrophilic copolymer (2) preferably have the samestructure. In the above embodiment, only one process is required tomanufacture the hydrophilic copolymer, and a use amount of thehydrophilic copolymer increases, which is therefore particularlypreferable from the viewpoints of the number of production steps duringmass production and a cost of products. Here, “the hydrophilic copolymer(1) and the hydrophilic copolymer (2) have the same structure” meansthat types of the structural units (A), (B), (C), and, if present, astructural unit derived from another monomer constituting thehydrophilic copolymer (1) are all the same as those of the structuralunits (A′), (B′), (C′), and, if present, a structural unit derived fromanother monomer constituting the hydrophilic copolymer (2), respectively(the hydrophilic copolymers (1) and (2) are constituted by the samestructural units). From the viewpoints of further improving theimmobilization strength (hence durability) between the adhesive layerand the surface lubricious layer, productivity, and the like, it ispreferable that the types and compositions (content ratio (molar ratio))of the structural units constituting the hydrophilic copolymers (1) and(2) are all the same (the hydrophilic copolymers (1) and (2) areconstituted by the same structural units and the same compositions).

In the surface lubricious layer, an abundance ratio (mixing ratio) ofthe hydrophilic copolymer (2) with respect to the polymer containing astructural unit derived from acrylamide is not particularly limited. Inthe surface lubricious layer, for the abundance ratio (mixing ratio) ofthe hydrophilic copolymer (2) with respect to the polymer containing astructural unit derived from acrylamide, the hydrophilic copolymer (2)is preferably 0.5 parts by weight or more and less than 500 parts byweight, more preferably 0.5 parts by weight to 450 parts by weight,still more preferably 0.5 parts by weight to 350 parts by weight, evenmore preferably 0.5 parts by weight to 200 parts by weight, yet stillmore preferably 0.5 parts by weight to 50 parts by weight, yet even morepreferably more than 0.5 parts by weight and less than 50 parts byweight, particularly preferably 0.8 parts by weight to 30 parts byweight, and most preferably more than 1 part by weight and 20 parts byweight or less with respect to 1 part by weight of the polymercontaining a structural unit derived from acrylamide. That is, in apreferred embodiment of the medical device, the hydrophilic copolymer(2) is contained in the surface lubricious layer at a ratio of 0.5 partsby weight or more and less than 500 parts by weight (more preferably 0.5parts by weight to 450 parts by weight, still more preferably 0.5 partsby weight to 350 parts by weight, even more preferably 0.5 parts byweight to 200 parts by weight, yet still more preferably 0.5 parts byweight to 50 parts by weight, yet even more preferably more than 0.5parts by weight and less than 50 parts by weight, particularlypreferably 0.8 parts by weight to 30 parts by weight, and mostpreferably more than 1 part by weight and 20 parts by weight or less)with respect to 1 part by weight of the polymer containing a structuralunit derived from acrylamide. With such an abundance ratio (mixingratio), the water retention effect of the polymer containing astructural unit derived from acrylamide and the lubricating property ofthe hydrophilic copolymer (2) can be exhibited in a good balance. Notethat when the surface lubricious layer contains two or more types ofpolymers containing a structural unit derived from acrylamide, the above“1 part by weight” means that a total amount of these polymerscontaining a structural unit derived from acrylamide is 1 part byweight. Similarly, when the surface lubricious layer contains two ormore types of hydrophilic copolymers (2), the above amount (part byweight) of the hydrophilic copolymer (2) means a total amount of thesehydrophilic copolymers (2). The above abundance ratio (mixing ratio) issubstantially equal to a ratio of a total charge amount (weight) of thehydrophilic copolymer (2) with respect to a total charge amount (weight)of the polymer containing a structural unit derived from acrylamideduring formation of the surface lubricious layer.

Here, the presence and the ratio (composition) of the structural unitderived from each polymerizable monomer in the hydrophilic copolymer (2)and the presence of the polymer containing a structural unit derivedfrom acrylamide in the surface lubricious layer can be confirmed by, forexample, analyzing peak intensity of a group contained in eachstructural unit using a known method such as IR, NMR, and pyrolysisGC/MS. In the present description, the presence and the ratio(composition) of the structural unit derived from each polymerizablemonomer in the hydrophilic copolymer (2) in the surface lubricious layercan be detected and measured by the same method as described above(Method for Detecting and Measuring Presence and Ratio of StructuralUnit Derived from Each Polymerizable Monomer in Hydrophilic Copolymer(1) in Adhesive Layer). The polymer containing a structural unit derivedfrom acrylamide in the surface lubricious layer can also be confirmed inthe same manner as described above (Method for Detecting and MeasuringPresence and Ratio of Structural Unit Derived from Each PolymerizableMonomer in Hydrophilic Copolymer (1) in Adhesive Layer). That is, in theabove method, a peak specific to a site specific to the polymercontaining a structural unit derived from acrylamide (for example, in¹H-NMR, a proton (hydrogen atom) of an amide group, or in ^(13C)-NMR, acarbon atom adjacent to an amide group) is to be confirmed, and whenthese peaks can be confirmed, it is determined that the polymercontaining a structural unit derived from acrylamide is present in thesample.

The abundance ratio (mixing ratio) of the hydrophilic copolymer (2) withrespect to the polymer containing a structural unit derived fromacrylamide in the surface lubricious layer can also be measured usingthe same known method as described above. In the present description,the abundance ratio (mixing ratio) of the hydrophilic copolymer (2) withrespect to the polymer containing a structural unit derived fromacrylamide in the surface lubricious layer is measured according to thefollowing method.

(Method for Measuring Abundance Ratio (Mixing Ratio) of HydrophilicCopolymer (2) with respect to Polymer Containing Structural Unit Derivedfrom Acrylamide in Surface Lubricious Layer)

With the surface of the medical device swollen with heavy water or thelike, precision diagonal cutting is performed on the medical device toprepare an inclined cross section of the medical device. From the crosssection, a surface lubricious layer portion located near the surface ofthe medical device is cut, and a material of the surface lubriciouslayer portion is collected. Next, the material of the surface lubriciouslayer portion is filled into a sample tube for solid NMR without any gapto prepare a sample and NMR measurement is performed. Here, aconcentration (concentration (c′)) of a site (for example, abenzophenone group) specific to the structural unit (C′) is measured. Aconcentration of the copolymer (concentration (c″)) is calculated basedon this concentration (c′) and the composition of the hydrophiliccopolymer (2). This concentration (c″) is regarded as an amount of thehydrophilic copolymer (2) in the surface lubricious layer. Separately,in the same manner, a concentration of a site specific to the polymercontaining a structural unit derived from acrylamide (for example, in¹H-NMR, a proton (hydrogen atom) of an amide group, or in ¹³C-NMR, acarbon atom adjacent to an amide group) (concentration (h)) is measured.This concentration (h) is regarded as an amount of the polymercontaining a structural unit derived from acrylamide in the surfacelubricious layer. A value obtained by dividing the concentration (c″) bythe concentration (h) (concentration (c″)/concentration (h)) is theabundance ratio (mixing ratio) of the hydrophilic copolymer (2) withrespect to the polymer containing a structural unit derived fromacrylamide in the surface lubricious layer. Note that an analyzer andmeasurement conditions used in the above measurement are as follows.

Analyzer: NM080006, manufactured by JEOL Ltd.

Measurement conditions: heavy water or a mixed liquid of heavy water anda heavy solvent of a lower alcohol.

Hereinafter, each polymerizable monomer constituting the hydrophiliccopolymer (2) contained in the surface lubricious layer according to thedisclosure will be described.

(Polymerizable Monomer (A′))

The hydrophilic copolymer (2) contains the structural unit derived fromthe polymerizable monomer (A′) having a sulfobetaine structure(structural unit (A′)). Here, the structural unit (A′) constituting thehydrophilic copolymer (2) may be one type alone or a combination of twoor more types. That is, the structural unit (A′) may be constituted byonly one type of structural unit (A′), or may be constituted by two ormore types of structural units (A′). Note that a plurality of structuralunits (A′) may be present in a block shape or in a random shape.

The polymerizable monomer (A′) (monomer A′) is a polymerizable monomerhaving a sulfobetaine structure. The sulfobetaine structure included inthe structural unit derived from the monomer A′ is excellent in effectof imparting the lubricating property. Therefore, the hydrophiliccopolymer (2) containing the structural unit derived from the monomer A′is considered to be excellent in lubricating property. A homopolymer ofthe monomer A′ is soluble in an aqueous NaCl solution, but is insolubleor difficult to dissolve in water or a lower alcohol. Therefore, it issuggested that the sulfobetaine structure may have a strongelectrostatic interaction. Therefore, a strong cohesive force actsinside the surface lubricious layer containing the hydrophilic copolymeraccording to the disclosure. Accordingly, the surface lubricious layeris considered to have high strength (excellent in durability). Note thatthe above is theory, and the invention is not limited to the abovetheory.

Since a specific definition and examples of the polymerizable monomer(A′) are the same as those (of Polymerizable Monomer (A)) in the aboveadhesive layer, description thereof will be omitted here.

From the viewpoint of further improving the lubricating property and thedurability (lubrication retaining property), the monomer A′ ispreferably a compound represented by the above formula (1). That is, ina preferred embodiment of the medical device, the polymerizable monomer(A′) is a compound represented by the above formula (1).

(Polymerizable Monomer (B′))

The hydrophilic copolymer (2) contains the structural unit derived fromthe polymerizable monomer (B′) having at least one group selected fromthe group consisting of a sulfonic acid group (—SO₃H), a sulfuric acidgroup (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof(structural unit (B′)). Here, the structural unit (B′) constituting thehydrophilic copolymer (2) may be one type alone or a combination of twoor more types. That is, the structural unit (B′) may be constituted byonly one type of structural unit (B′), or may be constituted by two ormore types of structural units (B′). Note that a plurality of structuralunits (B′) may be present in a block shape or in a random shape.

The polymerizable monomer (B′) (monomer B′) is a polymerizable monomerhaving at least one group selected from the group consisting of asulfonic acid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurousacid group (—OSO₂H), and salt groups thereof. By introducing such agroup, anionization occurs in an aqueous solvent, and electrostaticrepulsion occurs between the hydrophilic copolymers. As a result, anelectrostatic interaction between the sulfobetaine structures and ahydrophobic interaction between the photoreactive groups in thehydrophilic copolymers are reduced. Therefore, the solvent solubility ofthe copolymer (particularly the solubility in water, a lower alcohol, ora mixed solvent of water and a lower alcohol) is improved. Thisimproving effect is particularly remarkable when the photoreactive groupof the monomer C′ is a benzophenone group. Since the benzophenone grouphas a plurality of aromatic rings, the benzophenone groups are likely toassociate with each other by a π-π interaction, which makes the polymerscontaining the benzophenone group to aggregate and insolubilize.Therefore, it is considered that by introducing the structural unitderived from the polymerizable monomer (B′), the electrostatic repulsionoccurs as described above, and the association between the benzophenonegroups is reduced, and thus the solubility or dispersibility of thepolymer is rapidly improved. Note that the above mechanism is theory,and the invention is not limited to the above theory. Alternatively,even when the monomer C′ has an ester group, the above improving effectcan be obtained satisfactorily.

Since a specific definition and examples of the polymerizable monomer(B′) are the same as those (of Polymerizable Monomer (B)) in the aboveadhesive layer, description thereof will be omitted here.

Among these, from the viewpoint of further improving the solventsolubility, the polymerizable monomer (B′) is preferably a compoundrepresented by the following formula (2), (3), or (4), and morepreferably a compound represented by the following formula (2). That is,in a preferred embodiment of the medical device, the polymerizablemonomer (B′) is a compound represented by the following formula (2),(3), or (4). In a more preferred embodiment of the medical device, thepolymerizable monomer (B′) is a compound represented by the followingformula (2). Note that since specific definitions of the formulas (2) to(4) are the same as those (of Polymerizable Monomer (B)) describedabove, description thereof will be omitted here.

In the above formula (2),

R²¹ represents a hydrogen atom or a methyl group,

Z² represents an oxygen atom or —NH—,

R²² represents a linear or branched alkylene group having 1 to 20 carbonatoms, and

X represents a group selected from the group consisting of a sulfonicacid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acidgroup (—OSO₂H), and salt groups thereof.

In the above formula (3),

R³¹ represents a hydrogen atom or a methyl group,

R³² represents a single bond or a linear or branched alkylene grouphaving 1 to 20 carbon atoms, and

X represents a group selected from the group consisting of a sulfonicacid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acidgroup (—OSO₂H), and salt groups thereof.

In the above formula (4),

R⁴¹ represents a hydrogen atom or a methyl group,

R⁴² represents a linear or branched alkylene group having 1 to 20 carbonatoms, and

X represents a group selected from the group consisting of a sulfonicacid group (—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acidgroup (—OSO₂H), and salt groups thereof.

(Polymerizable Monomer (C′))

The hydrophilic copolymer (2) contains the structural unit derived fromthe polymerizable monomer (C′) having a photoreactive group (structuralunit (C′)). Here, the structural unit (C′) constituting the hydrophiliccopolymer (2) may be one type alone or a combination of two or moretypes. That is, the structural unit (C′) may be constituted by only onetype of structural unit (C′), or may be constituted by two or more typesof structural units (C′). Note that a plurality of structural units (C′)may be present in a block shape or in a random shape.

The polymerizable monomer (C′) (monomer C′) is a polymerizable monomerhaving a photoreactive group. With the polymer monomer C′, the surfacelubricious layer containing the hydrophilic copolymer (2) can be firmlyimmobilized on the substrate layer via the adhesive layer. Therefore,the medical device can exhibit sufficient durability (lubricationretaining property).

Since a specific definition and examples of the polymerizable monomer(C′) are the same as those (of Polymerizable Monomer (C)) in the aboveadhesive layer, description thereof will be omitted here.

From the viewpoints of forming a covalent bond with the adhesive layerand firm immobilization on the substrate layer, the photoreactive groupof the polymerizable monomer (C′) is preferably the same as thephotoreactive group of the polymerizable monomer (C) in the hydrophiliccopolymer (1) contained in the adhesive layer. That is, in a preferredembodiment of the medical device, the polymerizable monomer (C′) has agroup having a benzophenone structure.

The hydrophilic copolymer (2) may contain a structural unit derived froma polymerizable monomer other than the above monomer A′, monomer B′, andmonomer C′ (hereinafter, also referred to as “other monomer”) in a rangethat does not impair the effects of the medical device. In thehydrophilic copolymer (2) according to the disclosure, a content of thestructural unit derived from the other monomer is preferably less than10 mol %, more preferably less than 5 mol %, and still more preferablyless than 1 mol % (lower limit: more than 0 mol %), with respect to 100mol %, which is the total of the structural units derived from all themonomers. Note that when the structural unit derived from the othermonomer is constituted by two or more types of structural units, acomposition of the above structural unit derived from the other monomeroccupies a ratio (molar ratio (mol %)) of all the structural unitsderived from the other monomer with respect to the total of thestructural units derived from all the monomers (100 mol %). Preferably,the hydrophilic copolymer (2) according to the disclosure is constitutedonly by the monomer A′, the monomer B′, and the monomer C′ (thecomposition of the other monomer=0 mol %). Note that the mol % issubstantially equivalent to a ratio of a charge amount (mol) of theother monomer with respect to the total charge amount (mol) of all themonomers in the production of the polymer.

A terminal end of the hydrophilic copolymer (2) is not particularlylimited and is appropriately defined depending on types of raw materialsto be used, and is usually a hydrogen atom. A structure of the copolymeris not particularly limited, and may be any of a random copolymer, analternating copolymer, a periodic copolymer, and a block copolymer.

A weight average molecular weight (Mw) of the hydrophilic copolymer (2)is preferably several thousand to several million, more preferably 1,000to 1,000,000, and particularly preferably 5,000 to 500,000. In thedisclosure, the “weight average molecular weight” shall be a valuemeasured by gel permeation chromatography (GPC) using polyethyleneglycol as a standard substance.

[Method for Manufacturing Hydrophilic Copolymer (2)]

A method for manufacturing the hydrophilic copolymer (2) is notparticularly limited, and specific description thereof is the same asthat in the [Method for Manufacturing Hydrophilic Copolymer (1)] in theabove adhesive layer, and thus the description is omitted here.

[Method for Manufacturing Medical Device]

A method for manufacturing the medical device according to thedisclosure is not particularly limited except that the adhesive layer isformed using the above hydrophilic copolymer (1) and the surfacelubricious layer is formed using the above hydrophilic copolymer (2) andpolymer containing a structural unit derived from acrylamide, and aknown method can be applied in the same manner or after appropriatemodification. For example, preferred is a method in which a coatingliquid is prepared by dissolving the hydrophilic copolymer (1) in asolvent, and is coated onto a substrate layer of the medical device toform an adhesive layer, and then a coating liquid is prepared bydissolving the hydrophilic copolymer (2) and the polymer containing astructural unit derived from acrylamide in a solvent, and is coated ontothe above adhesive layer to form a surface lubricious layer. That is,the disclosure also provides the method for manufacturing the medicaldevice. The method includes coating a coating liquid (1) containing thehydrophilic copolymer (1) onto the substrate layer to form an adhesivelayer, and coating a coating liquid (2) containing the polymercontaining a structural unit derived from acrylamide and the hydrophiliccopolymer (2) onto the adhesive layer to form a surface lubriciouslayer. With such a method, the lubricating property and the durability(lubrication retaining property) can be imparted to the surface of themedical device.

(Coating Step for Adhesive Layer)

In the above method, the solvent used for dissolving the hydrophiliccopolymer (1) is preferably water, a lower alcohol, or a mixed solventof water and a lower alcohol from the viewpoints of working safety (lowtoxicity) and solubility. Here, the lower alcohol refers to a primaryalcohol having 1 to 3 carbon atoms, that is, methanol, ethanol,n-propanol, or isopropanol. The above lower alcohols may be used aloneor in combination of two or more types thereof.

A concentration of the hydrophilic copolymer (1) in the coating liquid(1) is not particularly limited, and is preferably 0.01 wt % to 50 wt %,more preferably 0.05 wt % to 40 wt %, and still more preferably 0.1 wt %to 30 wt %. Within such a range, coatability of the coating liquid (1)is good, and the obtained adhesive layer has sufficient lubricatingproperty and durability (lubrication retaining property). A uniformadhesive layer having a desired thickness can be easily obtained withsingle coating. Therefore, the hydrophilic copolymer (1) can form astrong and uniform chemical bond with the substrate layer by subsequentirradiation with active energy rays (immobilizing step for adhesivelayer). The range is also preferred in terms of production efficiency.Note that when the concentration of the hydrophilic copolymer (1) isless than 0.01 wt %, a sufficient amount of the hydrophilic copolymer(1) may not be immobilized on the surface of the substrate layer. Whenthe concentration of the hydrophilic copolymer (1) is more than 50 wt %,the viscosity of the coating liquid (1) may become too high to obtainthe adhesive layer having a uniform thickness. However, even when theconcentration deviates from the above range, the coating liquid (1) canbe sufficiently used as long as the function and effect of the medicaldevice are not influenced.

A coating amount of the coating liquid (1) is not particularly limited,and is preferably an amount that corresponds to the thickness of theabove adhesive layer.

Before coating the coating liquid (1), the surface of the substratelayer may be treated in advance by an ultraviolet irradiation treatment,a plasma treatment, a corona discharge treatment, a flame treatment, anoxidation treatment, a silane coupling treatment, a phosphoric acidcoupling treatment, or the like. When the solvent of the coating liquid(1) is only water, it is difficult to coat the coating liquid (1) ontothe surface of the hydrophobic substrate layer, and the surface of thesubstrate layer is made hydrophilic by performing a plasma treatment onthe surface of the substrate layer. Accordingly, wettability of thecoating liquid (1) to the surface of the substrate layer is improved,and a uniform adhesive layer can be formed. By applying the abovetreatment to the surface of the substrate layer, which does not have anyC—H bond of a metal, a fluorine resin, or the like, a covalent bond withthe photoreactive group of the hydrophilic copolymer (1) can be formed.

A method for coating the coating liquid (1) onto the surface of thesubstrate layer is not particularly limited, and a known method in therelated art can be applied, such as a coating printing method, a dippingmethod (dipping method, dip coating method), a spraying method (spraymethod), a spin coating method, and a mixed solution impregnated spongecoating method. Among these, a dipping method (dipping method, dipcoating method) is preferred.

(Drying Step for Adhesive Layer)

It is preferable that, after coating the coating liquid (1) containingthe hydrophilic copolymer (1) according to the disclosure onto thesurface of the substrate layer as described above, the substrate layeris taken out from the coating liquid (1), and a coating film is dried.Drying conditions are not particularly limited as long as the solventcan be removed from the coating film, and a warm air treatment may beperformed using a dryer or the like, or natural drying may be performed.A pressure condition during the drying is also not limited at all, andthe drying may be performed under a normal pressure (atmosphericpressure), or under a pressure or a reduced pressure. As a drying unit(device), for example, an oven, a decompression dryer, or the like canbe used, and in the case of natural drying, no drying unit (device) isparticularly required.

(Immobilizing Step for Adhesive Layer)

The coating film after the above drying step is irradiated with activeenergy rays. Accordingly, the photoreactive group in the coating film(the monomer C of the hydrophilic copolymer (1)) is activated, and achemical bond is formed between the photoreactive group and an alkylgroup (hydrocarbon group) contained in the substrate layer. Morespecifically, a case of a combination of the photoreactive group havinga benzophenone structure and a resin (a material having a hydrocarbongroup) constituting the substrate layer will be described. When thehydrophilic copolymer (1) has the photoreactive group having abenzophenone structure, two radicals are generated in the photoreactivegroup by irradiation with ultraviolet rays. One of these radicalsabstracts the hydrogen atom from the alkyl group (hydrocarbon group) inthe resin, and instead one radical is generated in the material. Then,the remaining radical in the photoreactive group and the radicalgenerated in the material are bonded to each other, whereby a covalentbond is formed between the photoreactive group of the hydrophiliccopolymer (1) in the adhesive layer and the material (resin) in thesubstrate layer. With such a chemical bond, the adhesive layercontaining the hydrophilic copolymer (1) is firmly immobilized on thesubstrate layer. Therefore, the adhesive layer can exhibit sufficientdurability (lubrication retaining property).

Examples of the active energy rays include ultraviolet rays (UV),electron beams, and gamma rays, and are preferably ultraviolet rays orelectron beams, and more preferably ultraviolet rays in consideration ofan influence on a human body. When the active energy rays areultraviolet rays, a wavelength at which the photoreactive group can beactivated can be appropriately selected as an irradiation wavelength.Specifically, a wavelength range of the ultraviolet rays is preferably200 nm to 400 nm, and more preferably 220 nm to 390 nm. The irradiationwith ultraviolet rays is preferably performed under a temperaturecondition of 10° C. to 100° C., and more preferably 20° C. to 80° C. Anirradiation intensity of the ultraviolet rays is not particularlylimited, and is preferably 1 mW/cm² to 5000 mW/cm², more preferably 10mW/cm² to 1000 mW/cm², and still more preferably 50 mW/cm² to 500mW/cm². An integrated light amount of the ultraviolet rays (anintegrated light amount of the ultraviolet rays on the adhesive layerbefore coating the surface lubricious layer) is not particularlylimited, and is preferably 100 mJ/cm² to 100,000 mJ/cm², and morepreferably 500 mJ/cm² to 50,000 mJ/cm². Examples of a device foremitting the ultraviolet rays include a high-pressure mercury lamp, alow-pressure mercury lamp, a metal halide lamp, a xenon lamp, and ahalogen lamp. Note that a method for emitting the active energy rays isnot particularly limited, and the irradiation may be performed from onedirection, or from multiple directions, or the irradiation may beperformed while rotating an irradiation source, or while rotating anobject to be irradiated (one in which the coating film of the adhesivelayer is formed on the substrate layer).

After performing the above irradiation with active energy rays, thecoating film may be washed with a solvent (for example, the solvent usedfor preparing the coating liquid (1)) to remove the unreactedhydrophilic copolymer (1).

The immobilization of the coating film (adhesive layer) on the substratelayer can be confirmed by using a known analytical method such as FT-IR,XPS, and TOF-SIMS. For example, the immobilization can be confirmed byperforming FT-IR measurement before and after the irradiation withactive energy rays and comparing ratios of a peak of bonds formed by theirradiation with active energy rays with respect to a peak of invariantbonds.

With the above method, in the medical device according to thedisclosure, the adhesive layer containing the hydrophilic copolymer (1)is formed on the surface of the substrate layer.

(Coating Step for Surface Lubricious Layer)

Here, the hydrophilic copolymer (2) and the polymer containing astructural unit derived from acrylamide are dissolved in a solvent toprepare the coating liquid (2), and the coating liquid (2) is coatedonto the adhesive layer formed as above. In the above method, thesolvent used for dissolving the hydrophilic copolymer (2) and thepolymer containing a structural unit derived from acrylamide ispreferably water, a lower alcohol, or a mixed solvent of water and alower alcohol from the viewpoints of working safety (low toxicity) andsolubility. Here, the lower alcohol refers to a primary alcohol having 1to 3 carbon atoms, that is, methanol, ethanol, n-propanol, orisopropanol. The above lower alcohols may be used alone or incombination of two or more types thereof. Here, the hydrophiliccopolymer (2) and the polymer containing a structural unit derived fromacrylamide may be added to the solvent together, may be sequentiallyadded to the same solvent (the hydrophilic copolymer (2) and then thepolymer containing a structural unit derived from acrylamide, or thepolymer containing a structural unit derived from acrylamide and thenthe hydrophilic copolymer (2)), or the hydrophilic copolymer (2) and thepolymer containing a structural unit derived from acrylamide may bedissolved in different solvents and then mixed with each other. Notethat when the hydrophilic copolymer (2) and the polymer containing astructural unit derived from acrylamide may be dissolved in differentsolvents, the solvents may be the same as or different from each other,and are preferably the same in consideration of ease of operation andthe like.

A concentration of the hydrophilic copolymer (2) in the coating liquid(2) is not particularly limited, and is preferably more than 0.05 wt %and less than 5 wt %, more preferably 0.1 wt % to 2.5 wt %, andparticularly preferably 0.1 wt % to 1.0 wt %. Within such a range,coatability of the coating liquid (2) is good, and a strong and uniformchemical bond can be formed with the adhesive layer (hydrophiliccopolymer (1)) or the polymer containing a structural unit derived fromacrylamide by subsequent irradiation with active energy rays(immobilizing step for surface lubricious layer) (therefore, the surfacelubricious layer has excellent lubricating property and durability(lubrication retaining property)). The range is also preferred in termsof production efficiency. A concentration of the polymer containing astructural unit derived from acrylamide in the coating liquid (2) is notparticularly limited, and is preferably more than 0.001 wt % and lessthan 5 wt %, more preferably 0.003 wt % to 3 wt %, still more preferably0.007 wt % to 0.5 wt %, even more preferably more than 0.01 wt % andless than 0.5 wt %, and particularly preferably 0.03 wt % to 0.3 wt %.Within such a range, the coatability of the coating liquid (2) is good,and the obtained surface lubricious layer can exhibit a sufficient waterretention effect (therefore, the surface lubricious layer can exhibit anexcellent lubricating property even under a high load condition). Here,a mixing ratio of the hydrophilic copolymer (2) with respect to thepolymer containing a structural unit derived from acrylamide in thecoating liquid (2) is not particularly limited, and is preferably thesame mixing ratio as described in the section of Surface LubriciousLayer.

A coating amount of the coating liquid (2) is not particularly limited,and is preferably an amount that corresponds to the thickness of theabove surface lubricious layer.

A method for coating the coating liquid (2) onto the surface of theadhesive layer is not particularly limited, and a known method in therelated art can be applied, such as a coating printing method, a dippingmethod (dipping method, dip coating method), a spraying method (spraymethod), a spin coating method, and a mixed solution impregnated spongecoating method. Among these, a dipping method (dipping method, dipcoating method) is preferred.

(Drying Step for Surface Lubricious Layer)

As described above, it is preferable that, after immersing the substratelayer on which the adhesive layer is formed in advance in the coatingliquid (2), the substrate layer is taken out from the coating liquid (2)and a coating film is dried. Drying conditions are not particularlylimited as long as the solvent can be removed from the coating film, anda warm air treatment may be performed using a dryer or the like, ornatural drying may be performed. A pressure condition during the dryingis also not limited at all, and the drying may be performed under anormal pressure (atmospheric pressure), or under a pressure or a reducedpressure. As a drying unit (device), for example, an oven, adecompression dryer, or the like can be used, and in the case of naturaldrying, no drying unit (device) is particularly required.

(Immobilizing Step for Surface Lubricious Layer)

The coating film after the above drying step is irradiated with activeenergy rays. Accordingly, the photoreactive group of the hydrophiliccopolymer (1) (monomer C) in the adhesive layer and the photoreactivegroup of the hydrophilic copolymer (2) (monomer C′) in the surfacelubricious layer are activated, and a chemical bond is formed betweenthe photoreactive group of the hydrophilic copolymer (1) and thephotoreactive group of the hydrophilic copolymer (2) and the polymercontaining a structural unit derived from acrylamide. For example, acase of a combination of the photoreactive group having a benzophenonestructure of the hydrophilic copolymer (1) in the adhesive layer and thephotoreactive group having a benzophenone structure of the hydrophiliccopolymer (2) and the polymer containing a structural unit derived fromacrylamide in the surface lubricious layer will be described. When thehydrophilic copolymers (1) and (2) have the photoreactive group having abenzophenone structure, two radicals are generated in the photoreactivegroup of each hydrophilic copolymer by the irradiation with ultravioletrays. One of these radicals abstracts the hydrogen atom from an alkylgroup (hydrocarbon group) in the polymer containing a structural unitderived from acrylamide, and instead one radical is generated in thepolymer containing a structural unit derived from acrylamide. Then, theremaining radical in the photoreactive group and the radical generatedin the polymer containing a structural unit derived from acrylamide arebonded to each other, whereby a covalent bond is formed between thephotoreactive group of the hydrophilic copolymer (1) in the adhesivelayer and the polymer containing a structural unit derived fromacrylamide in the surface lubricious layer, or between the photoreactivegroup of the hydrophilic copolymer (2) and the polymer containing astructural unit derived from acrylamide in the surface lubricious layer.With such a chemical bond between the polymer containing a structuralunit derived from acrylamide and the hydrophilic copolymer in theadhesive layer or the surface lubricious layer, the surface lubriciouslayer is firmly immobilized on the adhesive layer, and at the same time,the polymer containing a structural unit derived from acrylamide isfirmly immobilized in the surface lubricious layer. In addition, one ofthe two radicals of the hydrophilic copolymer (1) generated by theirradiation with the ultraviolet rays abstracts the hydrogen atom froman alkyl group (hydrocarbon group) in the hydrophilic copolymer (2), andinstead one radical is generated in the hydrophilic copolymer (2). Then,the remaining radical in the photoreactive group of the hydrophiliccopolymer (1) and the radical generated in the hydrophilic copolymer (2)are bonded to each other, whereby a covalent bond is formed between thephotoreactive group of the hydrophilic copolymer (1) in the adhesivelayer and the hydrophilic copolymer (2) in the surface lubricious layer.Similarly, one of the two radicals of the hydrophilic copolymer (2)generated by the irradiation with the ultraviolet rays abstracts thehydrogen atom from an alkyl group (hydrocarbon group) in the hydrophiliccopolymer (1), and instead one radical is generated in the hydrophiliccopolymer (1). Then, the remaining radical in the photoreactive group ofthe hydrophilic copolymer (2) and the radical generated in thehydrophilic copolymer (1) are bonded to each other, whereby a covalentbond is formed between the photoreactive group of the hydrophiliccopolymer (1) in the adhesive layer and the hydrophilic copolymer (2) inthe surface lubricious layer. With such a chemical bond between thehydrophilic copolymer (1) in the adhesive layer and the hydrophiliccopolymer (2) in the surface lubricious layer, the surface lubriciouslayer is also firmly immobilized on the adhesive layer. Therefore, thesurface lubricious layer can effectively exhibit the water retentioneffect of the polymer containing a structural unit derived fromacrylamide and can exhibit an excellent lubricating property. The waterretention effect of the polymer containing a structural unit derivedfrom acrylamide can be maintained for a long period of time, and theexcellent durability (lubrication retaining property) can also beexhibited.

Examples of the active energy rays include ultraviolet rays (UV),electron beams, and gamma rays, and are preferably ultraviolet rays orelectron beams, and more preferably ultraviolet rays in consideration ofan influence on a human body. When the active energy rays areultraviolet rays, a wavelength at which the photoreactive group can beactivated can be appropriately selected as an irradiation wavelength.Specifically, a wavelength range of the ultraviolet rays is preferably200 nm to 400 nm, and more preferably 220 nm to 390 nm. The irradiationwith ultraviolet rays is preferably performed under a temperaturecondition of 10° C. to 100° C., and more preferably 20° C. to 80° C. Anirradiation intensity of the ultraviolet rays is not particularlylimited, and is preferably 1 mW/cm² to 5000 mW/cm², more preferably 10mW/cm² to 1000 mW/cm², and still more preferably 50 mW/cm² to 500mW/cm². An integrated light amount of the ultraviolet rays (anintegrated light amount of the ultraviolet rays on the surfacelubricious layer) is not particularly limited, and is preferably 100mJ/cm² to 100,000 mJ/cm², and more preferably 500 mJ/cm² to 50,000mJ/cm². Examples of a device for emitting the ultraviolet rays include ahigh-pressure mercury lamp, a low-pressure mercury lamp, a metal halidelamp, a xenon lamp, and a halogen lamp. Note that a method for emittingthe active energy rays is not particularly limited, and the irradiationmay be performed from one direction, or from multiple directions, or theirradiation may be performed while rotating an irradiation source, orwhile rotating an object to be irradiated (one in which the coating filmof the adhesive layer is formed on the substrate layer).

After performing the above irradiation with active energy rays, thecoating film may be washed with a solvent (for example, the solvent usedfor preparing the coating liquid (2)) to remove the unreactedhydrophilic copolymer (2).

The immobilization of the coating film (surface lubricious layer) on theadhesive layer can be confirmed by using a known analytical method suchas FT-IR, XPS, and TOF-SIMS. For example, the immobilization can beconfirmed by performing FT-IR measurement before and after theirradiation with active energy rays and comparing ratios of a peak ofbonds formed by the irradiation with active energy rays with respect toa peak of invariant bonds.

With the above method, in the medical device according to thedisclosure, the surface lubricious layer containing the hydrophiliccopolymer (2) and the polymer containing a structural unit derived fromacrylamide is formed on the surface of the adhesive layer.

[Use of Medical Device]

The medical device disclosed here can be used in contact with a bodyfluid, blood, and the like. The surface thereof has a lubricatingproperty in an aqueous liquid such as a body fluid or physiologicalsaline, and can enhance operability and reduce damage to tissue mucosa.Specific examples include a catheter, a stent, and a guide wire to beused in blood vessels. That is, in one embodiment, the medical device isa catheter, a stent, or a guide wire. The medical device is alsoexemplified by the following.

(a) Catheters to be orally or nasally inserted or allowed to indwell ina digestive organ, such as stomach tube catheters, feeding catheters,and tubes for tube feeding.

(b) Catheters to be orally or nasally inserted or allowed to indwell ina respiratory tract or trachea, such as oxygen catheters, oxygencannulas, tubes and cuffs of tracheal tubes, tubes and cuffs oftracheotomy tubes, and tracheal aspiration catheters.

(c) Catheters to be inserted or allowed to indwell in a urethra orureter, such as urethra catheters, urinary catheters, and catheters andballoons of urethra balloon catheters.

(d) Catheters to be inserted or allowed to indwell in various lumens inliving bodies, organs, and tissues, such as suction catheters, draincatheters, and rectum catheters.

(e) Catheters to be inserted or allowed to indwell in a blood vessel,such as indwelling needles, IVH catheters, thermodilution catheters,angiography catheters, vasodilation catheters, and dilators orintroducers, or guide wires, stylets, and the like for the catheters.

(f) Artificial tracheae, artificial bronchi, and the like.

(g) Medical devices for extracorporeal circulation therapy (artificiallungs, artificial hearts, artificial kidneys, and the like) and circuitstherefor.

EXAMPLES

Hereinafter, the invention will be specifically described with referenceto Examples, but the invention is not limited to these Examples. Notethat parts and % in Examples are all by weight. In the followingexamples, unless otherwise defined, conditions for allowing to stand atroom temperature are all at 23° C. and 55% RH.

Production Example 1: Production of Hydrophilic Copolymer (A)

In 10 mL of a 2,2,2-trifluoroethanol/water (9/1 v/v) mixed solvent, 1.82g (6.5 mmol) of[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide(MSPB) manufactured by Sigma-Aldrich Co. LLC., 1.46 g (3.2 mmol) of a 50wt % aqueous solution of sodium 2-acrylamide-2-methyl-1-propanesulfonate(AMPS(Na)) manufactured by Sigma-Aldrich Co. LLC., and 0.080 g (0.3mmol) of 4-methacryloyloxybenzophenone (MBP) manufactured by MCC UNITECHCo., Ltd. were dissolved to prepare a reaction solution. Next, thereaction solution was charged into a 30 mL eggplant-shaped flask, oxygenwas removed by sufficient nitrogen bubbling, 2.8 mg (0.010 mmol) of apolymerization initiator 4,4′-azobis(4-cyanovaleric acid) was added,followed by immediate sealing, and polymerization was carried out in awater bath at 75° C. for 3 hours. Next, the solution was subjected toreprecipitation in acetone, and the supernatant was removed bydecantation to obtain a copolymer (A).

The composition of the obtained copolymer (A) wasMSPB:AMPS(Na):MPB=65:32:3 in terms of mol %. Here, the obtainedcopolymer (A) corresponds to the hydrophilic copolymer (1) contained inthe adhesive layer according to the disclosure and the hydrophiliccopolymer (2) contained in the surface lubricious layer according to thedisclosure. The weight average molecular weight (Mw) of the obtainedcopolymer (A) was measured by GPC, and was 180,000 in terms ofpolyethylene glycol.

Production Example 2: Production of Hydrophilic Copolymer (B)

In 10 mL of a 2,2,2-trifluoroethanol/water (9/1 v/v) mixed solvent, 1.99g (6.5 mmol) of a[3-(methacryloylamino)propyl]dimethyl(3-sulfobutyl)ammonium hydroxideinner salt (MSBB) manufactured by FUJIFILM Wako Pure ChemicalCooperation, 1.46 g (3.2 mmol) of a 50 wt % aqueous solution of sodium2-acrylamide-2-methyl-1-propanesulfonate (AMPS(Na)) manufactured bySigma-Aldrich Co. LLC., and 0.080 g (0.3 mmol) of4-methacryloyloxybenzophenone (MBP) manufactured by MCC UNITECH Co.,Ltd. were dissolved to prepare a reaction solution. Next, the reactionsolution was charged into a 30 mL eggplant-shaped flask, oxygen wasremoved by sufficient nitrogen bubbling, 2.8 mg (0.010 mmol) of apolymerization initiator 4,4′-azobis(4-cyanovaleric acid) was added,followed by immediate sealing, and polymerization was carried out in awater bath at 75° C. for 3 hours. Next, the solution was subjected toreprecipitation in acetone, and the supernatant was removed bydecantation to obtain a copolymer (B).

The composition of the obtained copolymer (B) wasMSBB:AMPS(Na):MPB=65:32:3 in terms of mol %. Here, the obtainedcopolymer (B) corresponds to the hydrophilic copolymer (1) contained inthe adhesive layer according to the disclosure and the hydrophiliccopolymer (2) contained in the surface lubricious layer according to thedisclosure. The weight average molecular weight (Mw) of the obtainedcopolymer (B) was measured by GPC, and was 190,000 in terms ofpolyethylene glycol.

Example 1

The copolymer (A) obtained in Production Example 1 (corresponding to thehydrophilic copolymer (1) according to the disclosure) was dissolved inethanol/water (3/7 w/w) so as to be 10 wt %, to prepare a coating liquid(1-A). Next, a polyamide tube (having an outer diameter of 2.4 mm and alength of 70 mm) was dipped in the coating liquid (1-A), and was takenout at a rate of 1 mm/sec. Next, the polyamide tube was dried at roomtemperature for 60 seconds to remove the solvent. Next, the polyamidetube was irradiated with ultraviolet rays (UV) having a wavelength of365 nm and an irradiation output of 105 mW/cm² under conditions of anirradiation distance of 250 mm and a sample rotation rate of 3 mm/secfor 3 minutes, so as to form an adhesive layer on the polyamide tube(polyamide tube (1-A)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.

Next, polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (numberaverage molecular weight (Mn)=150,000) was dissolved in water so as tobe 0.1 wt % and the copolymer (A) obtained in Production Example 1(corresponding to the hydrophilic copolymer (2) according to thedisclosure) was dissolved in water so as to be 1 wt %, to prepare acoating liquid (1′). A mixing ratio (weight ratio) of polyacrylamide tothe hydrophilic copolymer (2) in the coating liquid (1′) is 1:10. Next,the polyamide tube (1-A) prepared above was dipped in the coating liquid(1′) and was taken out at a rate of 5 mm/sec. Next, the polyamide tube(1-A) was dried at room temperature for 60 seconds to remove thesolvent. Next, the polyamide tube (1-A) was irradiated with ultravioletrays (UV) having a wavelength of 365 nm and an irradiation output of 105mW/cm² under conditions of an irradiation distance of 250 mm and asample rotation rate of 3 mm/sec for 3 minutes, so as to form a surfacelubricious layer on the adhesive layer of the polyamide tube (1-A)(polyamide tube (1′)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.A mixing ratio (weight ratio) of polyacrylamide to the hydrophiliccopolymer (2) in the surface lubricious layer of the polyamide tube (1′)is 1:10.

Next, the obtained polyamide tube (1′) was evaluated for the lubricatingproperty and durability (lubrication retaining property) using afriction meter (Handy Tribo Master TL201 manufactured by Trinity-LabInc.) 20 shown in FIG. 3 according to the following method. Results areshown in FIG. 4.

That is, a core material 18 was inserted into the above sample(polyamide tube (1′)) to prepare a sample 16. The sample 16 was laiddown in a length direction and fixed in a petri dish 12, and wasimmersed in physiological saline 17 having a depth that the entiresample 16 was immersed in the physiological saline. The petri dish 12was placed on a moving table 15 of the friction meter 20 shown in FIG.3. A silicon terminal (diameter: 10 mm) 13 was brought into contact withthe sample 16, and a load 14 of 450 g was applied onto the terminal.While the moving table 15 was subjected to 10 horizontal reciprocationsunder a sliding distance set to 25 mm and a sliding rate set to 16.7mm/sec, a sliding resistance value (gf) was measured. During thereciprocations from the first time to 10th time, an average of thesliding resistance values on a forward way for each reciprocation wastaken and plotted on a graph as a test force to thereby evaluate avariation in sliding resistance value during the 10 repeated slides.

Comparative Example 1

The copolymer (A) obtained in Production Example 1 (corresponding to thehydrophilic copolymer (1) according to the disclosure) was dissolved inethanol/water (3/7 w/w) so as to be 10 wt %, to prepare a coating liquid(1-A). Next, a polyamide tube (having an outer diameter of 2.4 mm and alength of 70 mm) was dipped in the coating liquid (1-A), and was takenout at a rate of 1 mm/sec. Next, the polyamide tube was dried at roomtemperature for 60 seconds to remove the solvent. Next, the polyamidetube was irradiated with ultraviolet rays (UV) having a wavelength of365 nm and an irradiation output of 105 mW/cm² under conditions of anirradiation distance of 250 mm and a sample rotation rate of 3 mm/secfor 3 minutes, so as to form a copolymer layer on the polyamide tube(comparative polyamide tube (1)). Note that as a UV irradiation device,ECE2000 (high pressure mercury lamp) manufactured by Dymax Corporationwas used. The comparative polyamide tube (1) has the same structure asthe polyamide tube (1′) in Example 1 except that the surface lubriciouslayer does not exist.

Next, the obtained comparative polyamide tube (1) was evaluated for thelubricating property and the durability (lubrication retaining property)in the same manner as in Example 1. Results are shown in FIG. 4.

According to FIG. 4, the polyamide tube (1′) according to the disclosurehas a low initial (the first reciprocation) sliding resistance value(excellent in lubricating property), and the sliding resistance valuethereof hardly changes until the 10th reciprocation (excellent indurability (lubrication retaining property)). In contrast, thecomparative polyamide tube (1) is excellent in durability (lubricationretaining property), but an initial sliding resistance value thereof ishigher than that of the polyamide tube (1′) according to the disclosure.This evaluation method is a method on assumption of a high loadcondition where a clearance between a catheter and an inner surface of alumen in a living body is small. That is, the sliding resistance valueis measured using the tube as a sample. The tube-shaped sample has acontact area with the terminal smaller than that of a sheet-shapedsample. Therefore, the tube-shaped sample has a force per unit areaapplied from the terminal (a larger load) larger than that of thesheet-shaped sample. Therefore, it is considered that the medical deviceaccording to the disclosure can exhibit excellent lubricating propertyand durability (lubrication retaining property) even under a high loadcondition where the clearance between the catheter and the inner surfaceof the lumen in the living body is small. Note that although thecomparative polyamide tube (1) in Comparative Example 1 has a slidingresistance value at an initial stage (the first reciprocation) and up tothe 10th reciprocation higher than that of the polyamide tube (1′)according to the disclosure, it is considered that the comparativepolyamide tube (1) also exhibits sufficient lubricating property anddurability (lubrication retaining property) under normal conditions.

Examples 2 to 6

Polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (number averagemolecular weight (Mn)=150,000) was dissolved in water so as to be 0.1 wt%, and the copolymer (A) obtained in Production Example 1 (correspondingto the hydrophilic copolymer (2) according to the disclosure) wasdissolved in water so as to be 5 wt % (coating liquid (2′)), 2.5 wt %(coating liquid (3′)), 0.5 wt % (coating liquid (4′)), 0.1 wt % (coatingliquid (5′)), and 0.05 wt % (coating liquid (6′)), to prepare coatingliquids (2′) to (6′). Mixing ratios (weight ratios) of polyacrylamide tothe hydrophilic copolymer (2) in the coating liquids (2′) to (6′) are1:50, 1:25, 1:5, 1:1, and 1:0.5, respectively.

Polyamide tubes (2′) to (6′) were prepared in the same manner as inExample 1 except that the coating liquids (2′) to (6′) prepared abovewere used instead of the coating liquid (1′) in Example 1. Here, mixingratios (weight ratios) of polyacrylamide to the hydrophilic copolymer(2) in the surface lubricious layer of the polyamide tubes (2′) to (6′)are 1:50, 1:25, 1:5, 1:1, and 1:0.5, respectively.

Next, the lubricating property (the sliding resistance value at thefirst reciprocation) of the obtained polyamide tubes (2′) to (6′) wasevaluated in the same manner as in Example 1. Results are shown in thefollowing Table 1. Note that in the following Table 1, the results ofComparative Example 1 are also shown. Evaluation criteria in thefollowing Table 1 are as follows. The lubricating property (the slidingresistance value at the first reciprocation) in Table 1 shows resultswhen the number of samples is 2 (n=2). When both samples are A, thelubricating property (the sliding resistance value at the firstreciprocation) is indicated as “A”, and when one sample is A and theother sample is B, the lubricating property (the sliding resistancevalue at the first reciprocation) is indicated as “B to A”.

(Evaluation Criteria)

A: The sliding resistance value at the first reciprocation is less than40% of that of Comparative Example 1.

B: The sliding resistance value at the first reciprocation is 40% ormore and less than 60% of that of Comparative Example 1.

C: The sliding resistance value at the first reciprocation is 60% ormore and less than 90% of that of Comparative Example 1.

D: The sliding resistance value at the first reciprocation is 90% ormore of that of Comparative Example 1.

TABLE 1 (Concentration of polyacrylamide: 0.1 wt %) Concentration Mixingratio (weight ratio) of (wt %) polyacrylamide: Lubricating property ofhydrophilic hydrophilic copolymer (sliding resistance value copolymer(2) (2) in surface lubricious layer at first reciprocation) 5 1:50 C 2.51:25 B 1 1:10 A 0.5 1:5 A 0.1 1:1 B to A 0.05 1:0.5 C — ComparativeExample 1 D

Examples 7 to 9

The copolymer (A) obtained in Production Example 1 (corresponding to thehydrophilic copolymer (2) according to the disclosure) was dissolved inwater so as to be 1 wt %, and polyacrylamide manufactured bySigma-Aldrich Co. LLC. (number average molecular weight (Mn)=150,000)was dissolved in water so as to be 0.01 wt % (coating liquid (7′)), 0.05wt % (coating liquid (8′)), and 1 wt % (coating liquid (9′)), to preparecoating liquids (7′) to (9′). Mixing ratios (weight ratios) ofpolyacrylamide to the hydrophilic copolymer (2) in the coating liquids(7′) to (9′) are 1:100, 1:20, and 1:1, respectively.

Polyamide tubes (7′) to (9′) were prepared in the same manner as inExample 1 except that the coating liquids (7′) to (9′) prepared abovewere used instead of the coating liquid (1′) in Example 1. Here, mixingratios (weight ratios) of polyacrylamide to the hydrophilic copolymer(2) in the surface lubricious layer of the polyamide tubes (7′) to (9′)are 1:100, 1:20, and 1:1, respectively.

Next, the lubricating property (the sliding resistance value at thefirst reciprocation) of the obtained polyamide tubes (7′) to (9′) wasevaluated in the same manner as in Example 1. Results are shown in thefollowing Table 2. Note that in the following Table 2, the results ofComparative Example 1 are also shown. Evaluation criteria in thefollowing Table 2 are the same as those in Table 1.

TABLE 2 (Concentration of hydrophilic copolymer (2): 1 wt %)Concentration Mixing ratio (weight ratio) of Lubricating property(sliding (wt %) of polyacrylamide:hydrophilic copolymer (2) inresistance polyacrylamide surface lubricious layer value at firstreciprocation) 0.01 1:100 C 0.05 1:20 A 0.1 1:10 A 1 1:1 B — ComparativeExample 1 D

Example 10

Polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (number averagemolecular weight (Mn) =40,000) was dissolved in water so as to be 0.1 wt% and the copolymer (A) obtained in Production Example 1 (correspondingto the hydrophilic copolymer (2) according to the disclosure) wasdissolved in water so as to be 1 wt %, to prepare a coating liquid(10′). A mixing ratio (weight ratio) of polyacrylamide to thehydrophilic copolymer (2) in the coating liquid (10′) is 1:10.

A polyamide tube (10′) was prepared in the same manner as in Example 1except that the coating liquid (10′) prepared above was used instead ofthe coating liquid (1′) in Example 1. Here, a mixing ratio (weightratio) of polyacrylamide to the hydrophilic copolymer (2) in the surfacelubricious layer of the polyamide tube (10′) is 1:10.

Next, the obtained polyamide tube (10′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was

Example 11

An acrylamide-acrylic acid-sodium acrylate copolymer (manufactured bySigma-Aldrich Co. LLC., product name: [poly(acrylamide-co-acrylic acid)partial sodium salt], number average molecular weight (Mn)=150,000, andacrylamide content=84 mol %) was dissolved in water so as to be 0.1 wt %and the copolymer (A) obtained in Production Example 1 (corresponding tothe hydrophilic copolymer (2) according to the disclosure) was dissolvedin water so as to be 1 wt %, to prepare a coating liquid (11′). A mixingratio (weight ratio) of the acrylamide-acrylic acid-sodium acrylatecopolymer to the hydrophilic copolymer (2) in the coating liquid (11′)is 1:10.

A polyamide tube (11′) was prepared in the same manner as in Example 1except that the coating liquid (11′) prepared above was used instead ofthe coating liquid (1′) in Example 1. Here, a mixing ratio (weightratio) of the acrylamide-sodium acrylate copolymer to the hydrophiliccopolymer (2) in the surface lubricious layer of the polyamide tube(11′) is 1:10.

Next, the obtained polyamide tube (11′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was “B”.

Example 12

The copolymer (B) obtained in Production Example 2 (corresponding to thehydrophilic copolymer (1) according to the disclosure) was dissolved inethanol/water (3/7 w/w) so as to be 10 wt %, to prepare a coating liquid(1-B). Next, a polyamide tube (having an outer diameter of 2.4 mm and alength of 70 mm) was dipped in the coating liquid (1-B), and was takenout at a rate of 1 mm/sec. Next, the polyamide tube was dried at roomtemperature for 60 seconds to remove the solvent. Next, the polyamidetube was irradiated with ultraviolet rays (UV) having a wavelength of365 nm and an irradiation output of 105 mW/cm² under conditions of anirradiation distance of 250 mm and a sample rotation rate of 3 mm/secfor 3 minutes, so as to form an adhesive layer on the polyamide tube(polyamide tube (1-B)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.

Next, polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (numberaverage molecular weight (Mn)=150,000) was dissolved in water so as tobe 0.1 wt % and the copolymer (B) obtained in Production Example 2(corresponding to the hydrophilic copolymer (2) according to thedisclosure) was dissolved in water so as to be 1 wt %, to prepare acoating liquid (12′). A mixing ratio (weight ratio) of polyacrylamide tothe hydrophilic copolymer (2) in the coating liquid (12′) is 1:10. Next,the polyamide tube (1-B) prepared above was dipped in the coating liquid(12′) and was taken out at a rate of 5 mm/sec. Next, the polyamide tube(1-B) was dried at room temperature for 60 seconds to remove thesolvent. Next, the polyamide tube (1-B) was irradiated with ultravioletrays (UV) having a wavelength of 365 nm and an irradiation output of 105mW/cm² under conditions of an irradiation distance of 250 mm and asample rotation rate of 3 mm/sec for 3 minutes, so as to form a surfacelubricious layer on the adhesive layer of the polyamide tube (1-B)(polyamide tube (12′)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.A mixing ratio (weight ratio) of polyacrylamide to the hydrophiliccopolymer (2) in the surface lubricious layer of the polyamide tube(12′) is 1:10.

Next, the obtained polyamide tube (12′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was “A”.

Example 13

Polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (number averagemolecular weight (Mn)=150,000) was dissolved in water so as to be 0.1 wt% and the copolymer (B) obtained in Production Example 2 (correspondingto the hydrophilic copolymer (2) according to the disclosure) wasdissolved in water so as to be 1 wt %, to prepare a coating liquid(13′). A mixing ratio (weight ratio) of polyacrylamide to thehydrophilic copolymer (2) in the coating liquid (13′) is 1:10.

A polyamide tube (13′) was prepared in the same manner as in Example 1except that the coating liquid (13′) prepared as above was used insteadof the coating liquid (1′) in Example 1. Here, a mixing ratio (weightratio) of polyacrylamide to the hydrophilic copolymer (2) in the surfacelubricious layer of the polyamide tube (13′) is 1:10.

Next, the obtained polyamide tube (13′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was “A”.

Example 14

Polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (number averagemolecular weight (Mn)=150,000) was dissolved in water so as to be 0.1 wt% and the copolymer (A) obtained in Production Example 1 (correspondingto the hydrophilic copolymer (2) according to the disclosure) wasdissolved in water so as to be 1 wt %, to prepare a coating liquid(14′). A mixing ratio (weight ratio) of polyacrylamide to thehydrophilic copolymer (2) in the coating liquid (14′) is 1:10.

A polyamide tube (14′) was prepared in the same manner as in Example 12except that the coating liquid (14′) prepared as above was used insteadof the coating liquid (12′) in Example 12. Here, a mixing ratio (weightratio) of polyacrylamide to the hydrophilic copolymer (2) in the surfacelubricious layer of the polyamide tube (14′) is 1:10.

Next, the obtained polyamide tube (14′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was “A”.

Example 15

The copolymer (A) obtained in Production Example 1 (corresponding to thehydrophilic copolymer (1) according to the disclosure) was dissolved inethanol/water (3/7 w/w) so as to be 7 wt %, to prepare a coating liquid(1-C). Next, a polyamide tube (having an outer diameter of 2.4 mm and alength of 70 mm) was dipped in the coating liquid (1-C), and was takenout at a rate of 1 mm/sec. Next, the polyamide tube was dried at roomtemperature for 60 seconds to remove the solvent. Next, the polyamidetube was irradiated with ultraviolet rays (UV) having a wavelength of365 nm and an irradiation output of 105 mW/cm² under conditions of anirradiation distance of 250 mm and a sample rotation rate of 3 mm/secfor 3 minutes, so as to form an adhesive layer on the polyamide tube(polyamide tube (1-C)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.

Next, polyacrylamide manufactured by Sigma-Aldrich Co. LLC. (numberaverage molecular weight (Mn)=150,000) was dissolved in water so as tobe 0.1 wt % and the copolymer (A) obtained in Production Example 1(corresponding to the hydrophilic copolymer (2) according to thedisclosure) was dissolved in water so as to be 1 wt %, to prepare acoating liquid (15′). A mixing ratio (weight ratio) of polyacrylamide tothe hydrophilic copolymer (2) in the coating liquid (15′) is 1:10. Next,the polyamide tube (1-C) prepared above was dipped in the coating liquid(15′) and was taken out at a rate of 5 mm/sec. Next, the polyamide tube(1-C) was dried at room temperature for 60 seconds to remove thesolvent. Next, the polyamide tube (1-C) was irradiated with ultravioletrays (UV) having a wavelength of 365 nm and an irradiation output of 105mW/cm² under conditions of an irradiation distance of 250 mm and asample rotation rate of 3 mm/sec for 3 minutes, so as to form a surfacelubricious layer on the adhesive layer of the polyamide tube (1-C)(polyamide tube (15′)). Note that as a UV irradiation device, ECE2000(high pressure mercury lamp) manufactured by Dymax Corporation was used.A mixing ratio (weight ratio) of polyacrylamide to the hydrophiliccopolymer (2) in the surface lubricious layer of the polyamide tube(15′) is 1:10.

Next, the obtained polyamide tube (15′) was evaluated for thelubricating property (the sliding resistance value at the firstreciprocation) in the same manner as in Example 1 and according to thesame evaluation criteria, and a result thereof was “A”.

The results of the above Examples and Comparative Examples aresummarized in the following Table 3. Note that in the following Table 3,the mixing ratio indicates a weight ratio of hydrophiliccopolymeracrylamide-based polymer in the surface lubricious layer.Columns for each hydrophilic copolymer and each acrylamide-based polymerindicate a concentration of each hydrophilic copolymer and eachacrylamide-based polymer in the coating liquid, and the lubricatingproperty means the lubricating property (the sliding resistance value atthe first reciprocation).

TABLE 3 Adhesive Layer Surface lubricious layer Lubri- HydrophilicHydrophilic Mixing cating copolymer copolymer Poly- weight prop- (A) (A)acrylamide ratio erty Example 10 1 0.1 10:1 A 1 wt % wt % Example 10 50.1 50:1 C 2 wt % wt % Example 10 2.5 0.1 25:1 B 3 wt % wt % Example 100.5 0.1 5:1 A 4 wt % wt % Example 10 0.1 0.1 1:1 B to A 5 wt % wt %Example 10 0.05 0.1 0.5:1 C 6 wt % wt % Example 10 1 0.01 100:1 C 7 wt %wt % Example 10 1 0.05 20:1 A 8 wt % wt % Example 10 1 1 1:1 B 9 wt % wt% Compar- 10 — — — D ative Example 1 Example 10 1 wt % 0.1 wt % 10:1 A10 Hydrophilic Hydrophilic Poly Mixing Lubri- copolymer copolymer(acrylamide- weight cating (A) (A) sodium ratio prop- acylate sodium)erty Example 10 1 wt % 0.1 wt % 10:1 B 11 Hydrophilic Hydrophilic Poly-Mixing Lubri- copolymer copolymer acrylamide weight cating (B) (B) ratioprop- erty Example 10 1 wt % 0.1 wt % 10:1 A 12 Hydrophilic HydrophilicPoly- Mixing Lubri- copolymer copolymer acrylamide weight cating (A) (B)ratio prop- erty Example 10 1 wt % 0.1 wt % 10:1 A 13 HydrophilicHydrophilic Poly- Mixing Lubri- copolymer copolymer acrylamide weightcating (B) (A) ratio prop- erty Example 10 1 wt % 0.1 wt % 10:1 A 14Hydrophilic Hydrophilic Poly- Mixing Lubri- copolymer copolymeracrylamide weight cating (A) (A) ratio prop- erty Example 7 1 wt % 0.1wt % 10:1 A 15

What is claimed is:
 1. A medical device, comprising: a substrate layer;an adhesive layer formed on at least a part of the substrate layer, theadhesive layer containing a hydrophilic copolymer (1) containing (i) astructural unit derived from a polymerizable monomer (A) having asulfobetaine structure, (ii) a structural unit derived from apolymerizable monomer (B) having at least one group selected from thegroup consisting of a sulfonic acid group, a sulfuric acid group, asulfurous acid group, and salt groups thereof, and (iii) a structuralunit derived from a polymerizable monomer (C) having a photoreactivegroup; and a surface lubricious layer formed on at least a part of theadhesive layer, the surface lubricious layer containing a polymer, saidpolymer containing (a) a structural unit derived from acrylamide, and(b) a hydrophilic copolymer (2) containing (i) a structural unit derivedfrom a polymerizable monomer (A′) having a sulfobetaine structure, (ii)a structural unit derived from a polymerizable monomer (B′) having atleast one group selected from the group consisting of a sulfonic acidgroup, a sulfuric acid group, a sulfurous acid group, and salt groupsthereof, and (iii) a structural unit derived from a polymerizablemonomer (C′) having a photoreactive group.
 2. The medical deviceaccording to claim 1, wherein the hydrophilic copolymer (2) is containedin the surface lubricious layer at a ratio of more than 0.5 parts byweight and less than 50 parts by weight with respect to 1 part by weightof the polymer containing the structural unit derived from acrylamide.3. The medical device according to claim 1, wherein the polymercontaining the structural unit derived from acrylamide ispolyacrylamide.
 4. The medical device according to claim 1, wherein thepolymerizable monomer (A) and/or (A′) is a compound represented by thefollowing formula (1):

in the above formula (1), R¹¹ represents a hydrogen atom or a methylgroup, Z¹ represents an oxygen atom or —NH—, R¹² and R¹⁵ eachindependently represent a linear or branched alkylene group having 1 to20 carbon atoms, and R¹³ and R¹⁴ each independently represent a linearor branched alkyl group having 1 to 20 carbon atoms.
 5. The medicaldevice according to claim 1, wherein the polymerizable monomer (B)and/or (B′) is a compound represented by the following formula (2), (3),or (4):

in the above formula (2), R²¹ represents a hydrogen atom or a methylgroup, Z² represents an oxygen atom or —NH—, R²² represents a linear orbranched alkylene group having 1 to 20 carbon atoms, and X represents agroup selected from the group consisting of a sulfonic acid group(—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof,

in the above formula (3), R³¹ represents a hydrogen atom or a methylgroup, R³² represents a single bond or a linear or branched alkylenegroup having 1 to 20 carbon atoms, and X represents a group selectedfrom the group consisting of a sulfonic acid group (—SO₃H), a sulfuricacid group (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groupsthereof, and

in the above formula (4), R⁴¹ represents a hydrogen atom or a methylgroup, R⁴² represents a linear or branched alkylene group having 1 to 20carbon atoms, and X represents a group selected from the groupconsisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof. 6.The medical device according to claim 1, wherein the polymerizablemonomer (C) and/or (C′) has a group having a benzophenone structure. 7.The medical device according to claim 1, wherein the hydrophiliccopolymer (1) and the hydrophilic copolymer (2) have the same structure.8. The medical device according to claim 1, wherein the medical deviceis a catheter, a stent, or a guide wire.
 9. The medical device accordingto claim 1, wherein the polymerizable monomer (A) and/or (A′) is acompound represented by the following formula (1):

in the above formula (1), R¹¹ represents a hydrogen atom or a methylgroup, Z¹ represents an oxygen atom or —NH—, R¹² and R¹⁵ eachindependently represent a linear or branched alkylene group having 1 to20 carbon atoms, and R¹³ and R¹⁴ each independently represent a linearor branched alkyl group having 1 to 20 carbon atoms; and wherein thepolymerizable monomer (B) and/or (B′) is a compound represented by thefollowing formula (2), (3), or (4):

in the above formula (2), R²¹ represents a hydrogen atom or a methylgroup, Z² represents an oxygen atom or —NH—, R²² represents a linear orbranched alkylene group having 1 to 20 carbon atoms, and X represents agroup selected from the group consisting of a sulfonic acid group(—SO₃H), a sulfuric acid group (—OSO₃H), a sulfurous acid group(—OSO₂H), and salt groups thereof,

in the above formula (3), R³¹ represents a hydrogen atom or a methylgroup, R³² represents a single bond or a linear or branched alkylenegroup having 1 to 20 carbon atoms, and X represents a group selectedfrom the group consisting of a sulfonic acid group (—SO₃H), a sulfuricacid group (—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groupsthereof, and

in the above formula (4), R⁴¹ represents a hydrogen atom or a methylgroup, R⁴² represents a linear or branched alkylene group having 1 to 20carbon atoms, and X represents a group selected from the groupconsisting of a sulfonic acid group (—SO₃H), a sulfuric acid group(—OSO₃H), a sulfurous acid group (—OSO₂H), and salt groups thereof. 10.The medical device according to claim 9, wherein the polymerizablemonomer (C) and/or (C′) has a group having a benzophenone structure. 11.The medical device according to claim 9, wherein the hydrophiliccopolymer (1) and the hydrophilic copolymer (2) have the same structure.12. The medical device according to claim 9, wherein the medical deviceis a catheter, a stent, or a guide wire.
 13. A method for manufacturinga medical device comprising: applying a coating liquid (1) onto asubstrate to form an adhesive layer on the substrate, the coating liquid(1) comprising: a hydrophilic copolymer (1) containing: i) a structuralunit derived from a polymerizable monomer (A) having a sulfobetainestructure; ii) a structural unit derived from a polymerizable monomer(B) having at least one group selected from the group consisting of asulfonic acid group, a sulfuric acid group, a sulfurous acid group, andsalt groups thereof; and iii) a structural unit derived from apolymerizable monomer (C) having a photoreactive group; and applying acoating liquid (2) onto the adhesive layer to form a surface lubriciouslayer, the coating liquid (2) comprising a polymer containing: (a) astructural unit derived from acrylamide; and (b) a hydrophilic copolymer(2), the hydrophilic copolymer (2) containing: i) a structural unitderived from a polymerizable monomer (A′) having a sulfobetainestructure; ii) a structural unit derived from a polymerizable monomer(B′) having at least one group selected from the group consisting of asulfonic acid group, a sulfuric acid group, a sulfurous acid group, andsalt groups thereof; and iii) a structural unit derived from apolymerizable monomer (C′) having a photoreactive group.
 14. The methodaccording to claim 13, wherein a concentration of the hydrophiliccopolymer (2) in the coating liquid (2) is 0.1 wt % to 2.5 wt %.
 15. Themethod according to claim 13, further comprising drying the coatingliquid (2) after the applying of the coating liquid (2) onto theadhesive layer.
 16. The method according to claim 15, further comprisingirradiating the coating liquid (2) to activate the photoreactive groupof the hydrophilic copolymer (1) and the photoreactive group of thehydrophilic copolymer (2), and form a chemical bond between thephotoreactive group of the hydrophilic copolymer (1) and thephotoreactive group of the hydrophilic copolymer (2) and the polymercontaining the structural unit derived from the acrylamide.
 17. Themethod according to claim 13, wherein the applying of the coating liquid(1) onto the substrate includes applying the coating liquid (1) onto acatheter, a stent, or a guide wire.
 18. A method comprising: inserting amedical device into a lumen in a living body, the medical devicecomprising: a substrate layer; an adhesive layer formed on at least apart of the substrate layer, the adhesive layer containing a hydrophiliccopolymer (1) containing (i) a structural unit derived from apolymerizable monomer (A) having a sulfobetaine structure, (ii) astructural unit derived from a polymerizable monomer (B) having at leastone group selected from the group consisting of a sulfonic acid group, asulfuric acid group, a sulfurous acid group, and salt groups thereof,and (iii) a structural unit derived from a polymerizable monomer (C)having a photoreactive group; and a surface lubricious layer formed onat least a part of the adhesive layer, the surface lubricious layercontaining a polymer, said polymer containing (a) a structural unitderived from acrylamide, and (b) a hydrophilic copolymer (2) containing(i) a structural unit derived from a polymerizable monomer (A′) having asulfobetaine structure, (ii) a structural unit derived from apolymerizable monomer (B′) having at least one group selected from thegroup consisting of a sulfonic acid group, a sulfuric acid group, asulfurous acid group, and salt groups thereof, and (iii) a structuralunit derived from a polymerizable monomer (C′) having a photoreactivegroup; and moving the medical device in the lumen in the living body,whereby aqueous liquid in the lumen contacts and wets the surfacelubricious layer so that the surface lubricious layer exhibits alubricating property.
 19. The method according to claim 18, wherein theinserting of the medical device into the lumen in the living bodyincludes inserting a catheter, a stent, or a guide wire into the lumenin the living body.
 20. The method according to claim 18, wherein thehydrophilic copolymer (2) is contained in the surface lubricious layerat a ratio of more than 0.5 parts by weight and less than 50 parts byweight with respect to 1 part by weight of the polymer containing thestructural unit derived from acrylamide.